Full research paper
The association of resistance trainingwith mortality: A systematic reviewand meta-analysis
Farzane Saeidifard1, Jose R Medina-Inojosa1, Colin P West2,3,Thomas P Olson1, Virend K Somers1, Amanda R Bonikowske1,Larry J Prokop4, Manlio Vinciguerra5 andFrancisco Lopez-Jimenez1
Abstract
Background: The benefits of aerobic exercise are well-studied; there is no consensus on the association between
resistance training and major adverse cardiovascular outcomes. This systematic review and meta-analysis aimed to
address this issue.
Design and methods: We searched for randomized trials and cohort studies that evaluated the association between
resistance training and mortality and cardiovascular events. Two investigators screened the identified abstracts and full-
texts independently and in duplicate. Cochrane tools were used to assess the risk of bias. We calculated hazard ratios
and 95% confidence intervals using random effect models.
Results: From the 1430 studies identified, 11 (one randomized trial and 10 cohort studies) met the inclusion criteria,
totaling 370,256 participants with mean follow-up of 8.85 years. The meta-analysis showed that, compared with no
exercise, resistance training was associated with 21% (hazard ratio (95% confidence interval (CI)), 0.79 (0.69–0.91)) and
40% (hazard ratio (95% CI), 0.60 (0.49–0.72)) lower all-cause mortality alone and when combined with aerobic exercise,
respectively. Furthermore, resistance training had a borderline association with lower cardiovascular mortality (hazard
ratio (95% CI), 0.83 (0.67–1.03)). In addition, resistance training showed no significant association with cancer mortality.
Risk of bias was low to intermediate in the included studies. One cohort study looked at the effect of resistance training
on coronary heart disease events in men and found a 23% risk reduction (risk ratio, 0.77, CI: 0.61–0.98).
Conclusion: Resistance training is associated with lower mortality and appears to have an additive effect when
combined with aerobic exercise. There are insufficient data to determine the potential beneficial effect of resistance
training on non-fatal events or the effect of substituting aerobic exercise with resistance training.
Keywords
Resistance training, strength training, mortality, cardiovascular outcome, systematic review, meta-analysis
Received 5 February 2019; accepted 23 April 2019
Introduction
Sedentary lifestyle is a risk factor for a shorter lifespan,adverse cardiovascular events and many other comor-bidities such as diabetes, hypertension, obesity andcancer.1,2 A range of physical activities, from standingand walking to performing moderate-to-vigorous phys-ical activities, reduce sedentary time and have beenindependently associated with longer life expectancyand improvement in quality-of-life,3 with lower ratesof multiple comorbidities and mortality.3–5 Physical
1Division of Preventive Cardiology, Department of Cardiovascular
Medicine, Mayo Clinic Rochester, USA2Division of General Internal Medicine, Mayo Clinic, Rochester, USA3Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester,
USA4Mayo Clinic Libraries, Mayo Clinic, Rochester, USA5International Clinical Research Center (ICRC), St. Anne’s University
Hospital, Brno, Czech Republic
Corresponding author:
Francisco Lopez-Jimenez, Division of Preventive Cardiology, Department
of Cardiovascular Medicine, Mayo Clinic, 200 First Street SW, Rochester,
MN 55905, USA.
Email: [email protected].
European Journal of Preventive
Cardiology
0(00) 1–19
! The European Society of
Cardiology 2019
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DOI: 10.1177/2047487319850718
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activity including endurance and resistance training mayalso improve clinical outcomes even in patients with car-diovascular or valvular heart disease.6,7 Most of the evi-dence for the benefits of substituting sedentary time withphysical activity has focused on testing the effect of aer-obic exercise on different health measures.8 Existing evi-dence overwhelmingly shows that aerobic exercisepositively affects health measures including increasinglifespan, reducing rates of cardiovascular events,improving metabolic health, and preventing manycomorbidities, while lowering healthcare costs.9,10
Another form of physical activity that can be used toreduce sedentary time is resistance training; however,whether resistance training shares the potential benefitsand positive long-term effects of aerobic exercise onhealth in general, and on cardiovascular events inparticular, is currently unclear. Resistance training nor-mally involves lifting weights (using either machines orfree weights) typically at loads greater than 65% of theone-repetition maximum, defined as the heaviest weighta person can lift with maximum effort in a single repe-tition.11 Resistance training is sub-divided into dynamicresistance training, involving concentric and/or eccen-tric contractions of muscles with changes in length andthe tension of the muscles, and static exertion or iso-metric resistance training, based on sustained musclecontraction against a fixed load or resistance with nochange in length of the muscles.12 Mechanistic studieshave shown that relatively short periods of resistancetraining could lead to improvements in a number ofcardiovascular risk factors including insulin resistance,glucose and lipid metabolism,5,11 and endothelial func-tion, with reduced sympathetic neural activation.13
Further, a small number of epidemiologic studies sug-gest a possible beneficial effect on survival,14–16 but theresults have been conflicting and inconclusive.
The present study aims to systematically review theassociation between resistance training and multipleoutcomes including all-cause mortality, cardiovascularmortality, cancer mortality, ischemic heart disease, andstroke, with a focus on comparisons between resistancetraining and no resistance training adjusted for aerobicexercise, and resistance training versus aerobic exercise.
Methods
We designed the protocol based on the CochraneHandbook of Systematic Reviews of Intervention andPreferred Reporting Items for Systematic Reviews andMeta-Analysis (PRISMA) statement, and the ScientificStatement from the American Heart Association onsystematic review and meta-analysis on cardiac preven-tion and treatment studies.17
We searched for randomized or quasi-randomizedtrials and cohort studies that compared resistance
training with aerobic exercise or no exercise, in the gen-eral adult population in terms of major cardiovascularoutcomes including all-cause mortality, cardiovascularmortality, cancer mortality, ischemic heart disease, andstroke. We did not exclude studies on the basis of theyear of publication, language, or length of follow-up;but we excluded studies with different designs oroutcomes.
We conducted a comprehensive search of severaldatabases from each database’s inception to 25September 2017. The databases included OvidMEDLINE Epub Ahead of Print, Ovid Medline In-Process & Other Non-Indexed Citations, OvidMEDLINE, Ovid EMBASE, Ovid Cochrane CentralRegister of Controlled Trials, Ovid CochraneDatabase of Systematic Reviews, and Scopus. Thesearch strategy was designed and conducted by anexperienced librarian (LJP) with input from thestudy’s lead investigators. We used controlled vocabu-lary supplemented with keywords to search for theassociation between resistance training and cardiovas-cular outcomes in adults (detailed strategy is availablein the Supplementary Material online). We renewed thesearch on 6 November 2018.
One investigator (FS) reviewed the references of theeligible studies to identify any additional studies thathad been missed by the original search. Additionally,the authors of the eligible studies were contacted byemail to identify any similar studies done by the sameauthor or other authors that were not found in theprimary search.
Having applied the search strategy and generated alist of potential studies, two investigators (FS andJRMI) conducted eligibility screening: first, by exclud-ing any papers that did not match the criteria of interestbased on the title and abstracts; and second, by review-ing their full text to evaluate their eligibility for inclu-sion in the final analysis. The entire screening processwas performed independently and in duplicate using thesystematic review software Covidence�.
Studies meeting all eligibility criteria underwent dataextraction for further analysis. When the investigatorsdisagreed on the inclusion or exclusion of a study, theywould discuss the case and attempt to resolve the issue;when a third opinion was needed the senior investigator(FLJ) would independently review the study and makea final decision.
The data abstraction included the general character-istics of the study (author, year of publication, studydesign), characteristics of the study participants(sample size, age, gender, and basic health status inboth intervention and control groups), characteristicsof the intervention and comparisons (type, frequency,and intensity of resistance training) and the duration offollow-up, and outcomes data (all-cause mortality,
2 European Journal of Preventive Cardiology 0(00)
cardiovascular mortality, cancer mortality, ischemicheart disease, and stroke). Data were collected by twoinvestigators (FS and JRMI) independently and induplicate. The authors of studies were contacted whenthe data needed in the analysis were not accessiblethrough the published version of the articles.
We used Cochrane tools for assessment of the risk ofbias in clinical trials and observational studies at bothstudy and outcome levels. The tool used for the clinicaltrials assessed the sequence generation, allocationconcealment, blinding, incomplete outcome data, andselective outcome reporting, and other sources of bias.The tool for evaluation of the observational studies(ROBINS-E) assessed different domains for any pos-sible bias.18,19 The domains for evaluating the risk ofbias are as follows: confounding bias, bias in selectionof the participants into the study, bias in classificationof exposures, bias due to departures from intendedexposures, bias due to missing data, bias in measure-ment of outcomes, bias in selection of the reportedresult, and overall risk of bias.
Since most of the included studies were derived fromNational Health and Nutritional Examination Survey(NHANES) and National Health Interview Survey(NHIS) surveys, we minimized the overlap between par-ticipants of the included papers in several ways. Toexclude the studies with overlap but not losing anyimportant data, we contacted the authors of the originalstudies, looking for data on specific subgroup analyses.We excluded studies that were conducted in the sametime frame and also those that had more than 10% over-lap in their study samples. Finally, when conductingsubgroup analyses we verified that no subgroups repre-senting the same population would be included.
The outcomes-of-interest in this study were countsand rates and reported mostly as hazard ratio or riskratio (RR) (from Cox regression model) and in onestudy as odds ratio (OR) (from logistic regressionmodel); we converted OR to RR ((RR¼OR/(1-preva-lence of the outcome in the reference group)þ (preva-lence of the outcome in the reference group)) andassumed the RR equivalent to hazard ratio for the ana-lysis. For analyses adjusted for covariates we used themost adjusted ratios, recognizing that those analyseswould adjust for similar but not identical potential con-founders. The majority of the multivariate analysesincluded for covariates age, gender, comorbidities(including hypertension, hyperlipidemia, and diabetesmellitus), body mass index, physical activities, aerobicexercise, smoking status, and diet.
To conduct a meta-analysis we used RevMan v.5.3and generic inverse variance model. To measure theheterogeneity between the individual studies for eachoutcome we used I2 statistics, deeming I2 values morethan 75% as considerable heterogeneity. Funnel plots
were used and visually inspected for assessing publica-tion bias.
We predefined different subgroup analyses based onfactors believed to affect the possible associationbetween resistance training and outcomes, such as:intensity, frequency (low: >2, moderate: 2–5 and high�5 sessions/week) and duration of the resistance train-ing, gender, presence or absence of hypertension, base-line health status of the participants, and patient orpopulation based studies. We also predefined a sub-group based on the level of adjustment of the analysiscomparing resistance training with the primary out-comes, dividing studies adjusted for multiple potentialconfounders versus those adjusted only for age and/orgender, or not adjusted.
Results
The primary search identified 1421 records and ninemore studies were found by searching the referencelists of the eligible studies. From these records, 11 studieswith a total of 370,256 participants met the inclusioncriteria for the systematic review and meta-analysis,from which eight were from the screening of the studiesidentified through the primary search and three werefrom those identified through hand-searching. Figure 1is a PRISMA diagram showing the details of each stageof the screening and eligibility assessment and also thereasons for the exclusion of the studies. Reviewers werein agreement over which studies should be included(j¼ 0.83).
Although the primary search included key termsfor major cardiovascular outcomes, the majority ofthe studies included in the final analysis assessed onlymortality (all-cause, cardiovascular, and cancer).
Table 1 shows the characteristics of the stu-dies14–16,20–27 in detail. One study was a randomizedclinical trial and the other studies were cohort studies,mostly focused on the data from the NHANES andNHIS. All of the studies except one were done in theUnited States. All of the included studies were pub-lished in English and one of the studies was not yetpublished by the time of the data extraction so itsdata were obtained through contacting the authors.20
The average follow-up was 8.85 years and the agerange was 18–75 years. Within-study risk of bias waslow to moderate (we considered a mild risk of bias forthe design of the included studies, which were mostlycohorts compared with a well-done randomized clinicaltrial) in all of the included studies, except one that wasmoderate. Table 2 shows the details of the risk of biasin different domains for each study.
The studies evaluating the association betweenresistance training and all-cause mortality included341,820 participants. The results are presented in
Saeidifard et al. 3
Figures 2–4: Figure 2(a) shows that performing anyfrequency of resistance training is associated with21% lower all-cause mortality in comparison with noexercise (hazard ratio (95% confidence interval (CI)),0.79 (0.69–0.91)). Based on the subgroup analysis, per-forming >0 to two sessions of resistance training perweek is associated with lower all-cause mortality (0.79(0.66–0.95)), but doing more than two sessions of resist-ance training is not (Figure 2(b)). These results wereunchanged after performing a sensitivity analysis thatrestricted the analysis to population based studies (datanot shown). Additionally, the results show that follow-ing the current recommendations by the AmericanCollege of Sport Medicine and the American HeartAssociation on performing 2–3 sessions of resistancetraining per week is not significantly better than per-forming lower frequencies of resistance training interms of all-cause mortality (1.00 (0.89–1.11)) (Figure2(c)).
Some studies included in this analysis also comparedaerobic exercise with no exercise21–24 and, as expected,they demonstrated that aerobic exercise is associatedwith lower all-cause mortality (0.59 (0.45–0.76) forany aerobic exercise versus no exercise21–24) with adose–response relationship (data not shown) (0.64(0.56–0.74) for 1–2 sessions of aerobic exercise22–24
and 0.56 (0.41–0.76) for� 2 sessions of aerobicexercise21–24).
Some studies tested the association between thecombination of resistance training and aerobic exerciseand all-cause mortality. As Figure 2(d) shows, the
combination of any frequency of resistance trainingwith any frequency of aerobic exercise compared withno exercise is associated with a significantly lower all-cause mortality (40%, 0.60 (0.49–0.72)).
The association between resistance training and car-diovascular mortality was tested in 122,671 participantsand revealed that performing resistance training had aborderline association with lower cardiovascular mor-tality (hazard ratio 0.83 (0.68–1.01)) (Figure 3(a)). Asshown in Figure 3(b) and (c), results suggested that nofrequency of resistance training has a significant asso-ciation with lower cardiovascular mortality. In con-trast, as Figure 3(d) shows, the combination of anyfrequency of resistance training with any frequency ofaerobic exercise compared with no exercise is signifi-cantly associated with lower cardiovascular mortality(0.43 (0.27–0.70)).
The result of the analysis of the data from 57,557participants testing the association between resistancetraining and cancer mortality shows no associationbetween resistance training and cancer mortality (0.81(0.54–1.20)) (Figure 4(a)), which was not affected byincreasing the frequency of resistance training in aweek (Figure 4(b)). Furthermore, the combination ofresistance training and aerobic exercise had no signifi-cant association with cancer mortality (Figure 4(c)).
We identified only one cohort study that investigatedthe association between resistance training and differenttypes of non-fatal events. The study followed 44,452 USmen for two years and defined coronary events as theoccurrence of fatal coronary heart disease and non-fatal myocardial infarctions (MIs). The results of thestudy showed a 23% (RR 0.77, CI: 0.61–0.98) riskreduction in men who trained with weights for 30minor more per week compared with men who did not trainwith weights.28 Two other cohort studies investigatedthe association between resistance training and all fataland non-fatal cardiovascular outcomes under a generaldefinition of ‘‘cardiovascular disease (CVD)’’ and didnot meet our inclusion criteria for the final analysisalthough they reported an association between resist-ance training and lower CVD.29
No study specifically assessed the associationbetween resistance training and cerebrovascularoutcomes.
Discussion
This study showed that performing resistance trainingis associated with lower all-cause mortality while it hasa borderline association with cardiovascular mortality.There is an additional lowering of risk seen amongthose performing resistance training along with aerobicexercise. By contrast, there is no association betweenresistance training and cancer mortality. Based on the
1421 studies identified throughdatabase searching
Nine additional studies identifiedthrough other sources
1430 studies after duplicates removed
27 studies screened Records excluded (n = 5)
for outcomes unrelated to the meta-analysis
22 of full-text articlesassessed for eligibility
11 of studies included in qualitative synthesis
Full-text articles excluded (n = 11)
due to study design
11 of studies included in quantitative synthesis
(meta-analysis)
1423 studies excluded
based on title and abstract
Iden
tific
atio
nS
cree
ning
Elig
ibili
tyIn
clud
ed
Figure 1. PRISMA flow diagram detailing the literature search,
with the number of included and excluded studies and reasons
for exclusion in each stage.
4 European Journal of Preventive Cardiology 0(00)
Tab
le1.
Char
acte
rist
ics
of
the
studie
sin
cluded
inth
esy
stem
atic
revi
ewan
dm
eta
-anal
ysis
of
the
asso
ciat
ion
betw
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resi
stan
cetr
ainin
gan
ddiff
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nt
card
iova
scula
routc
om
es.
Firs
t
auth
or
Year
of
public
atio
n
Study
desi
gnN
Mean
follo
w-u
p
(year
s)
Sett
ing
(PIC
O)
(pat
ient,
inte
rvention/e
xposu
re,
com
par
ison,outc
om
e)
Fact
ors
adju
sted
for
Loca
tion
of
the
study
Courn
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21
2014
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dom
ized
tria
l
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om
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us
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ntr
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hyp
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on,
card
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illness
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dpsy
chia
tric
illness
or
were
oth
erw
ise
not
clear
ed
by
their
onco
logi
st
None
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Saeidifard et al. 5
Tab
le1.
Continued
Firs
t
auth
or
Year
of
public
atio
n
Study
desi
gnN
Mean
follo
w-u
p
(year
s)
Sett
ing
(PIC
O)
(pat
ient,
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rvention/e
xposu
re,
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par
ison,outc
om
e)
Fact
ors
adju
sted
for
Loca
tion
of
the
study
Dan
kel2
02017
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2773
9.7
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icip
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ts:In
div
idual
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year
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activi
ties
desi
gned
tost
rengt
hen
your
musc
les,
such
aslif
ting
weig
hts
,push
-ups
or
sit-
ups?
’’as
the
num
ber
ofse
lf-re
port
ed
sess
ions
com
ple
ted
within
the
pas
t30
day
s
Co
mp
ari
son
:not
meeting
the
guid
elin
efo
rm
usc
le
stre
ngt
henin
gac
tivi
ties
Age
,se
x,ra
ce/e
thnic
ity,
edu-
cational
,m
arri
ed,ci
gare
tte
smokin
g,in
tera
ctio
n
betw
een
curr
ent
em
plo
y-
ment
and
follo
w-u
ptim
e,
need
speci
alequip
ment
to
wal
k,ar
thri
tis,
cance
r,
body
mas
sin
dex,in
ter-
action
betw
een
body
mas
s
index
cate
gori
es
and
follo
w-u
ptim
e,
hypert
en-
sion
pre
hypert
ensi
on,an
d
dia
bete
s,pre
dia
bete
s,
oth
er
PA/s
edenta
rybehav
-
ior
com
ponents
.
The
United
Stat
es
(continued)
6 European Journal of Preventive Cardiology 0(00)
Tab
le1.
Continued
Firs
t
auth
or
Year
of
public
atio
n
Study
desi
gnN
Mean
follo
w-u
p
(year
s)
Sett
ing
(PIC
O)
(pat
ient,
inte
rvention/e
xposu
re,
com
par
ison,outc
om
e)
Fact
ors
adju
sted
for
Loca
tion
of
the
study
Ou
tco
mes:
all-ca
use
and
card
iova
scula
rm
ort
ality
adju
sted
for
age,
sex,ra
ce/e
thnic
ity,
educa
tional
leve
l,m
arital
stat
us,
smokin
gst
atus,
em
plo
yment,
the
need
for
speci
al
equip
ment
tow
alk,ar
thri
tis,
and
cance
r
Exclu
sio
n:Lim
ited
the
sam
ple
topar
tici
pan
tsw
ho
wer
e40
year
sofag
eor
old
eran
dex
cluded
per
sons
who
wer
enot
elig
ible
for
mort
ality
linka
ge.Par
tici
pan
tsw
ere
aske
d
whet
her
adoct
or
or
hea
lth
pro
fess
ional
ever
told
them
that
they
had
ahis
tory
of
angi
na,
coro
nar
yhea
rtdis
ease
,
conge
stiv
ehea
rtfa
ilure
,m
yoca
rdia
lin
farc
tion,or
stro
ke.
Par
tici
pan
tsw
ere
clas
sifie
das
hav
ing
pre
vale
nt
CV
Dif
they
answ
ered
‘‘yes’
’to
any
of
thes
efiv
eques
tions
and
wer
efu
rther
excl
uded
,al
though
inse
nsi
tivi
tyan
alys
es
thes
epar
tici
pan
tsw
ere
inco
rpora
ted.To
acco
unt
for
pre
vale
nt
conditio
ns
that
mig
ht
affe
ctPA
leve
lsan
dse
d-
enta
rybeh
avio
r,th
eyex
cluded
par
tici
pan
tsw
ho
die
din
the
first
two
year
soffo
llow
-up.
They
also
excl
uded
those
who
eith
erdid
not
wea
rth
eac
cele
rom
eter
or
whose
acce
lero
met
erw
asfo
und
tonot
be
inca
libra
tion
upon
retu
rnor
was
faulty.
Furt
her
limited
the
cohort
by
excl
udin
gper
sons
who
did
not
pro
vide
adher
ent
dat
a.
Las
tly,
excl
uded
those
who
wer
em
issi
ng
dat
aon
self-
report
edPA
or
any
pote
ntial
confo
under
left
inth
efin
al
model
s.
Grø
ntv
ed
25
2012
Cohort
32,0
02
18
Part
icip
an
ts:m
en
from
the
Heal
th
Pro
fess
ional
sFo
llow
-up
Study
Exp
osu
re:m
usc
le-s
trengt
henin
gac
tivi
ties
atbas
elin
e.T
he
par
tici
pan
tsre
port
ed
their
avera
gew
eekly
amount
of
weig
ht
trai
nin
g,oth
er
phys
ical
activi
ties
Co
mp
ari
son
:not
meeting
the
guid
elin
efo
rm
usc
le
stre
ngt
henin
gac
tivi
ties
Ou
tco
mes:
risk
of
type
2dia
bete
s,al
l-ca
use
and
card
io-
vasc
ula
rm
ort
ality
adju
sted
for
age,sm
okin
g,al
cohol
consu
mption,co
ffee
inta
ke,ra
ce,
fam
ilyhis
tory
of
dia
-
bete
s,in
take
of
tota
lenerg
y,tr
ans
fat,
poly
unsa
tura
ted
fat
tosa
tura
ted
fat
ratio,ce
real
fiber,
whole
grai
n,an
d
glyc
em
iclo
ad,ae
robic
exerc
ise,oth
er
PAof
atle
ast
modera
tein
tensi
ty,an
dT
Vvi
ewin
g
Age
,sm
okin
g,al
coholco
n-
sum
ption,co
ffee
inta
ke,
race
,fa
mily
his
tory
of
dia
-
bete
s,in
take
of
tota
l
energ
y,tr
ans
fat,
poly
un-
satu
rate
dfa
tto
satu
rate
d
fat
ratio,ce
real
fiber,
whole
grai
n,an
dgl
ycem
ic
load
,ae
robic
exerc
ise,
oth
er
PAof
atle
ast
mod-
era
tein
tensi
ty,an
dT
V
view
ing,
body
mas
sin
dex
The
United
Stat
es
(continued)
Saeidifard et al. 7
Tab
le1.
Continued
Firs
t
auth
or
Year
of
public
atio
n
Study
desi
gnN
Mean
follo
w-u
p
(year
s)
Sett
ing
(PIC
O)
(pat
ient,
inte
rvention/e
xposu
re,
com
par
ison,outc
om
e)
Fact
ors
adju
sted
for
Loca
tion
of
the
study
Exclu
sio
n:excl
uded
those
men
who
report
ed
ahis
tory
of
dia
bete
s,ca
nce
r,m
yoca
rdia
lin
farc
tion
angi
na,
coro
nar
y
arte
rybyp
ass
graf
t,oth
er
hear
tco
nditio
ns,
stro
ke,or
pulm
onar
yem
bolis
mon
the
bas
elin
equest
ionnai
re
(1986)
and
in1988,an
d1990.
Har
dee
26
2014
Cohort
2863
7.3
Part
icip
an
ts:ca
nce
rsu
rviv
ors
aged
18–81
year
s,both
mal
ean
dfe
mal
e,
who
rece
ived
apre
ventive
medic
al
exam
inat
ion
while
enro
lled
inth
eA
ero
bic
sC
ente
r
Longi
tudin
alSt
udy
inD
alla
s,Te
xas
Exp
osu
re:�
1se
ssio
nofm
usc
le-s
trengt
henin
gac
tivi
ties
at
bas
elin
ew
hic
hw
asas
sess
ed
by
self-
report
on
the
med-
ical
his
tory
quest
ionnai
re.Par
tici
pan
tsw
ere
aske
dto
pro
vide
yes/
no
answ
ers
toth
efo
llow
ing
quest
ions:
1).
‘‘Are
you
curr
ently
invo
lved
ina
musc
le-s
trengt
henin
g
pro
gram
?’’2
).‘‘C
anyo
usp
eci
fyth
em
usc
le-s
trengt
henin
g
activi
tyas
‘Cal
isth
enic
s’,‘F
ree
Weig
hts
’,‘W
eig
ht
Tra
inin
g
Mac
hin
es’
,or
‘Oth
er’
?’’3
).‘‘H
ow
man
yday
sper
week
do
you
do
these
exerc
ises?
’’T
hose
that
resp
onded
‘‘Yes’
’to
free
weig
hts
or
weig
ht
trai
nin
gan
dhad
exerc
ised
atle
ast
one
day
per
week
were
clas
sifie
das
posi
tive
for
musc
le-
stre
ngt
henin
gac
tivi
ty
Co
mp
ari
son
:no
musc
lest
rengt
henin
gac
tivi
ties
inth
e
pas
t30
day
s
Ou
tco
mes:
all-ca
use
and
card
iova
scula
rm
ort
ality
adju
sted
by
age,ge
nder,
body
mas
sin
dex,cu
rrent
smokin
g,heav
y
dri
nkin
g,hy
pert
ensi
on,dia
bete
s,hy
perc
hole
stero
lem
ia,
and
par
enta
lhis
tory
of
cance
r
Exclu
sio
n:Par
tici
pan
tsw
ere
excl
uded
from
the
final
ana-
lysi
sif
they
were
underw
eig
ht
(body
mas
sin
dex<
18.5
);
report
ed
myo
card
ialin
farc
tion
or
stro
ke;die
dduri
ng
first
year
offo
llow
-up;or
had
mis
sing
dat
aon
resi
stan
ce
exerc
ise
or
PA
Age
,ge
nder,
exam
inat
ion
year
,body
mas
sin
dex,
curr
ent
smokin
g,heav
y
dri
nkin
g,hy
pert
ensi
on,
dia
bete
s,hy
perc
hole
ster-
ole
mia
,an
dpar
enta
lhis
-
tory
ofca
nce
r,le
isure
-tim
e
aero
bic
phy
sica
lac
tivi
ty,
resi
stan
ceexerc
ise
The
United
Stat
es
(continued)
8 European Journal of Preventive Cardiology 0(00)
Tab
le1.
Continued
Firs
t
auth
or
Year
of
public
atio
n
Study
desi
gnN
Mean
follo
w-u
p
(year
s)
Sett
ing
(PIC
O)
(pat
ient,
inte
rvention/e
xposu
re,
com
par
ison,outc
om
e)
Fact
ors
adju
sted
for
Loca
tion
of
the
study
Kam
ada2
32017
Cohort
28,8
79
12
Part
icip
an
ts:par
tici
pan
tsof
Wom
en’s
Heal
thSt
udy
(fem
ale)
who
were
free
of
card
iova
scula
rdis
eas
e,
dia
-
bete
sm
elli
tus,
and
cance
rw
ith
avera
gebas
elin
eag
eof
62.2
year
s
Exp
osu
re:m
usc
le-s
trengt
henin
gac
tivi
ties
atbas
elin
e.
A
stre
ngt
htr
ainin
gquest
ionnai
rew
asin
cluded:‘‘D
uri
ng
the
pas
tm
onth
,w
hat
was
your
appro
xim
ate
tim
eper
week
spent
ateac
hof
the
follo
win
gre
creat
ional
activ-
itie
s?W
eig
ht
lifting/
stre
ngt
htr
ainin
g.’’
Co
mp
ari
son
:no
musc
lest
rengt
henin
gac
tivi
ties
inth
e
pas
t30
day
s
Ou
tco
mes:
all-ca
use
,ca
rdio
vasc
ula
r,an
dca
nce
rm
ort
ality
adju
sted
for
age
and
tria
lran
dom
izat
ion,r
ace,educa
tion,
post
menopau
salst
atus,
horm
one
use
,sm
okin
gst
atus,
par
enta
lhis
tory
of
myo
card
ialin
farc
tion
or
cance
r,
alco
holin
take
,energ
yin
take
,sa
tura
ted
fat
inta
ke,fib
er
inta
ke,fr
uit
and
vege
table
inta
ke,phy
sica
lexam
inat
ion
for
scre
enin
g,an
dtim
eper
week
spent
inae
robic
modera
teto
vigo
rous
PA(f
or
stre
ngt
htr
ainin
gan
dvi
ce
vers
a),body
mas
sin
dex
and
inci
dence
of
hypert
ensi
on,
hig
hch
ole
stero
l,ca
rdio
vasc
ula
rdis
eas
es,
dia
bete
sm
elli
-
tus,
and
cance
rbefo
rean
dduri
ng
follo
w-u
p
Exclu
sio
n:w
eexcl
uded
wom
en
with
mis
sing
info
rmat
ion
on
PAth
en,an
dw
om
en
dia
gnose
das
hav
ing
CV
D
(myo
card
ialin
farc
tion,s
troke
,perc
uta
neous
tran
slum
inal
coro
nar
yan
giopla
sty,
or
coro
nar
yar
tery
byp
ass
graf
t-
ing)
,ca
nce
r,or
dia
bete
sm
elli
tus
befo
reth
e96-m
onth
quest
ionnai
re
Age
,tr
ialra
ndom
izat
ion,
race
,educa
tion,post
me-
nopau
salst
atus,
horm
one
use
,sm
okin
gst
atus,
par
-
enta
lhis
tory
of
myo
card
ial
infa
rction
or
cance
r,al
co-
holin
take
,energ
yin
take
,
satu
rate
dfa
tin
take
,fib
er
inta
ke,fr
uit
and
vege
table
inta
ke,phy
sica
lexam
in-
atio
nfo
rsc
reenin
g,tim
e
per
week
spent
inae
robic
modera
teto
vigo
rous
PA,
body
mas
sin
dex,i
nci
dence
of
hypert
ensi
on,hig
h
chole
stero
l,ca
rdio
vasc
ula
r
dis
eas
es,
dia
bete
sm
elli
tus,
and
cance
rbefo
rean
d
duri
ng
follo
w-u
p
Kra
schnew
ski2
72016
Cohort
25,6
63
15
Part
icip
an
ts:in
div
idual
s�
65
year
s,both
men
and
wom
en,fr
om
the
1997–2001
NH
IS
Exp
osu
re:m
usc
le-s
trengt
henin
gac
tivi
ties
atbas
elin
eth
at
was
asse
ssed
usi
ng
the
follo
win
gquest
ion:‘‘H
ow
oft
en
do
you
do
leis
ure
-tim
ephy
sica
lac
tivi
ties
speci
fical
ly
desi
gned
tost
rengt
hen
your
musc
les,
such
aslif
ting
weig
ht
or
doin
gca
listh
enic
s?’’
Par
tici
pan
tre
sponse
s
incl
uded
both
the
num
ber
oftim
es
stre
ngt
htr
ainin
gw
as
perf
orm
ed
and
the
unit
of
tim
e(i.e
.‘‘p
er
week,’’
‘‘per
month
’’).
Age
,ge
nder,
race
/eth
nic
ity,
educa
tional
stat
us,
mar
ital
stat
us,
body
mas
sin
dex,
PA,al
coholuse
,sm
okin
g,
dia
bete
sm
elli
tus,
hyper-
tensi
on,co
ronar
yhear
t
dis
eas
e,
non-s
kin
cance
r
The
United
Stat
es
(continued)
Saeidifard et al. 9
Tab
le1.
Continued
Firs
t
auth
or
Year
of
public
atio
n
Study
desi
gnN
Mean
follo
w-u
p
(year
s)
Sett
ing
(PIC
O)
(pat
ient,
inte
rvention/e
xposu
re,
com
par
ison,outc
om
e)
Fact
ors
adju
sted
for
Loca
tion
of
the
study
Co
mp
ari
son
:not
meeting
the
guid
elin
efo
rm
usc
le
stre
ngt
henin
gac
tivi
ties
Ou
tco
mes:
all-ca
use
mort
ality
adju
sted
for
age,ge
nder,
eth
nic
ity,
educa
tional
stat
us,
mar
ital
stat
us,
body
mas
s
index,PA
,al
coholuse
,sm
okin
gst
atus,
dia
bete
s,hy
per-
tensi
on,co
ronar
yhear
tdis
eas
e,
non-s
kin
cance
rs
Lopri
nzi
14
2015
Cohort
12,3
21
4.8
Part
icip
an
ts:i
ndiv
idual
sw
ith
mean
age
of45.0
year
s,both
men
and
wom
en,fr
om
the
1999–2004
NH
AN
ES
Exp
osu
re:m
usc
le-s
trengt
henin
gac
tivi
ties
atbas
elin
e.
Indiv
idual
sse
lf-re
port
ed
their
invo
lvem
ent
inm
usc
le-
stre
ngt
henin
gac
tivi
ties
atth
ein
itia
lbas
elin
eas
sess
ment
by
resp
ondin
gto
two
quest
ions:
‘‘Ove
rth
epas
t30
day
s,
did
you
do
any
phy
sica
lac
tivi
ties
speci
fical
lydesi
gned
to
stre
ngt
hen
your
musc
les,
such
aslif
ting
weig
ht,
push
-ups
or
sit-
ups?
’’;an
dif
so‘‘O
ver
the
pas
t30
day
s,how
man
y
tim
es
did
you
do
these
activi
ties
desi
gned
tost
rengt
hen
your
musc
les,
such
aslif
ting
weig
hts
,push
-ups
or
sit-
ups?
’’as
the
num
ber
ofse
lf-re
port
ed
sess
ions
com
ple
ted
within
the
pas
t30
day
s
Co
mp
ari
son
:not
hav
ing
musc
lest
rengt
henin
gac
tivi
ties
in
the
pas
t30
day
s
Ou
tco
mes:
all-ca
use
mort
ality
and
card
iova
scula
rm
or-
talit
yad
just
ed
for
age,ge
nder,
race
–eth
nic
ity,
body
mas
s
index,an
dC
RP
Exclu
sio
n:excl
udin
gpar
tici
pan
tsw
ith
mis
sing
dat
aon
the
move
ment
bas
ed
behav
iors
,th
ose
with
mis
sing
cova
riat
e
dat
a,th
ose
with
mis
sing
mort
ality
stat
us
or
dura
tion
to
follo
w-u
p
Age
,ge
nder,
race
–eth
nic
ity,
body
mas
sin
dex,an
dC
RP
The
United
Stat
es
Schoenborn
15
2011
Cohort
242,3
97�
7P
art
icip
an
ts:in
div
idual
sag
ed�
18
year
s,both
men
and
wom
en,fr
om
the
1997–2004
NH
IS
Exp
osu
re:m
usc
le-s
trengt
henin
gac
tivi
ties
atbas
elin
eas
the
num
ber
of
self-
report
ed
sess
ions
com
ple
ted
within
the
pas
t30
day
sby
askin
g:H
ow
oft
en
do
you
do
LEIS
UR
E-T
IME
phys
ical
activi
ties
speci
fıca
llydesi
gned
to
STR
EN
GT
HEN
your
musc
les
such
aslif
ting
weig
hts
or
doin
gca
listh
enic
s?
Co
mp
ari
son
:not
meeting
the
guid
elin
efo
rm
usc
le
stre
ngt
henin
gac
tivi
ties
Gender,
continuous
age,r
ace/
eth
nic
ity,
educa
tion,pov-
ert
yst
atus,
heal
thin
sur-
ance
stat
us,
body
mas
s
index,sm
okin
g,an
dco
n-
sum
ption
of
alco
holan
d
were
stra
tifie
dby
the
pre
sence
/abse
nce
of
sele
cted
chro
nic
heal
th
conditio
ns.
The
United
Stat
es
(continued)
10 European Journal of Preventive Cardiology 0(00)
Tab
le1.
Continued
Firs
t
auth
or
Year
of
public
atio
n
Study
desi
gnN
Mean
follo
w-u
p
(year
s)
Sett
ing
(PIC
O)
(pat
ient,
inte
rvention/e
xposu
re,
com
par
ison,outc
om
e)
Fact
ors
adju
sted
for
Loca
tion
of
the
study
Ou
tco
mes:
all-ca
use
mort
ality
adju
sted
for
gender,
con-
tinuous
age,ra
ce/e
thnic
ity,
educa
tion,pove
rty
stat
us,
heal
thin
sura
nce
stat
us,
body
mas
sin
dex,sm
okin
g,
consu
mption
of
alco
hol,
and
chro
nic
heal
thco
nditio
n
Exclu
sio
n:excl
udin
gca
ses
whose
funct
ional
limitat
ions
may
be
the
resu
ltof
their
close
ness
todeat
h
Zhao
24
2013
Cohort
10,5
35
4.8
Part
icip
an
ts:in
div
idual
sag
ed�
20
year
s,both
men
and
wom
en,fr
om
the
1999
to2004
NH
AN
ES
Exp
osu
re:m
usc
le-s
trengt
henin
gac
tivi
ties
atbas
elin
e.
Indiv
idual
sse
lf-re
port
ed
their
invo
lvem
ent
inm
usc
le-
stre
ngt
henin
gac
tivi
ties
atth
ein
itia
lbas
elin
eas
sess
ment
by
resp
ondin
gto
two
quest
ions:
‘‘Ove
rth
epas
t30
day
s,
did
you
do
any
phy
sica
lac
tivi
ties
speci
fical
lydesi
gned
to
stre
ngt
hen
your
musc
les,
such
aslif
ting
weig
ht,
push
-ups
or
sit-
ups?
’’;an
dif
so‘‘O
ver
the
pas
t30
day
s,how
man
y
tim
es
did
you
do
these
activi
ties
desi
gned
tost
rengt
hen
your
musc
les,
such
aslif
ting
weig
hts
,push
-ups
or
sit-
ups?
’’as
the
num
ber
ofse
lf-re
port
ed
sess
ions
com
ple
ted
within
the
pas
t30
day
s
Co
mp
ari
son
:not
meeting
the
guid
elin
efo
rm
usc
le
stre
ngt
henin
gac
tivi
ties
Ou
tco
mes:
all-ca
use
and
card
iova
scula
rm
ort
ality
adju
sted
for
sex,ra
ce/e
thnic
ity,
educa
tion,body
weig
ht
stat
us,
smokin
g,heav
yal
coholdri
nkin
g,se
rum
conce
ntr
atio
ns
of
tota
lch
ole
stero
lan
dhig
h-d
ensi
tylip
opro
tein
chole
s-
tero
l,ele
vate
dC
RP,
eG
FR,pre
-exis
ting
chro
nic
condi-
tions
(hyp
ert
ensi
on,dia
bete
sm
elli
tus,
card
iova
scula
r
dis
eas
e,as
thm
a,ar
thri
tis,
dis
abili
ty,an
dca
nce
r)an
dty
pe
of
PA(a
ero
bic
and
resi
stan
ce)
Exclu
sio
n:e
xcl
uded
wom
en
who
report
ed
bein
gpre
gnan
t,
adults
who
had
mis
sing
resp
onse
sto
the
quest
ions
on
leis
ure
-tim
ePA
or
musc
le-s
trengt
henin
gac
tivi
tyan
d
adults
with
unas
cert
ained
surv
ival
stat
us
and
those
with
mis
sing
valu
es
for
study
cova
riat
es
Age
,se
x,ra
ce/e
thnic
ity,
edu-
cation,body
weig
ht
stat
us,
smokin
g,heav
yal
cohol
dri
nkin
g,se
rum
conce
n-
trat
ions
of
tota
lch
ole
s-
tero
lan
dhig
h-d
ensi
ty
lipopro
tein
chole
stero
l,
ele
vate
dC
RP,
eG
FR,pre
-
exis
ting
chro
nic
conditio
ns
(hyp
ert
ensi
on,dia
bete
s
melli
tus,
card
iova
scula
r
dis
eas
e,
asth
ma,
arth
ritis,
dis
abili
ty,an
dca
nce
r),ae
r-
obic
PA
The
United
Stat
es
CR
P:C
-reac
tive
pro
tein
;C
VD
:ca
rdio
vasc
ula
rdis
eas
e;eG
FR:est
imat
ed
glom
eru
lar
filtr
atio
nra
te;N
HA
NES:
Nat
ional
Heal
than
dN
utr
itio
nal
Exam
inat
ion
Surv
ey;N
HIS
:N
atio
nal
Heal
thIn
terv
iew
Surv
ey;
PA:phy
sica
lac
tivi
ty
Saeidifard et al. 11
results of the study, only one cohort study looked at theassociation between resistance training and each non-fatal cardiovascular events also showing a lower risk ofMI among those performing resistance training.
The associations between resistance training andall-cause and also borderline association with cardio-vascular mortality could be explained by the multiplebeneficial changes that occur with resistance training,related to changes in body composition and glucosemetabolism and to the neuro-humoral system: resist-ance training decreases abdominal fat and specificallyvisceral fat, decreases the android-to-gynoid fat ratio,increases lean mass, prevents the development of sarco-penic obesity and slows muscle loss.5,11,30 This is key
because total body fat, and abdominal fat in particular,plays a pivotal role in facilitating the development ofmultiple kinds of chronic diseases such as obesity, type2 diabetes mellitus (T2DM) and cardiovascular condi-tions;8,11 all major contributors to a lower lifespan.On the other hand, obesity itself is associated withdysregulation of fatty acid metabolism resulting inaccumulation of lipid in the skeletal muscle cells,which increases insulin resistance.5 Resistance trainingalso decreases inflammatory products, likely as a reflec-tion of changes in body composition.5,31 Becauseinflammatory mediators increase the risk of CVD,metabolic syndrome, and T2DM, the effect of resist-ance training on reducing these mediators would at
Table 2. Risk of bias in different domainsa and overall risk of bias in different studies that were included in the systematic review and
meta-analysis of the association between resistance training and mortality (all-cause, cardiovascular, and cancer).
First author
Sequence
allocation
Allocation
concealment Blinding
Incomplete
outcome
data
Selective
outcome
reporting
Other sources
of bias
Overall
risk
of bias
Courneya21
Confounding Participants Classification
of interventions
Deviations
from intended
interventions
Missing
data
Measurement
of the outcome
Selection
of the
reported
result
Overall
riskb
of bias
Dankel 201616
Dankel 201720
Evenson22
Grøntved25
Hardee26
Kamada23
Kraschnewski27
Loprinzi14
Schoenborn15
Zhao24
aDifferent colors show different amount of risk of bias within different domains: green represents a low risk of bias, yellow represents an unclear risk of
bias or not enough information is provided in the study to make a judgment and red represents serious-to-critical risk of bias within each domain.bShows the overall risk of bias in different studies in the range of low to critical (low, moderate, serious, and critical risk of bias). Green shows a low
risk of bias and yellow shows a moderate risk of bias.
12 European Journal of Preventive Cardiology 0(00)
Courneya 2014Hardee 2014Loprinzi 2015Kamada 2017Dankel 2016Grøntved 2012
Grøntved 2012
Grøntved 2012
Total (95% CI)
Total (95% CI)
Heterogeneity: Tau2 = 0.01; Chi2 = 18.66, df = 5 (P = 0.002); I2 = 73%Test for overall effect: Z = 3.31 (P = 0.0009)
Kamada 2017
Dankel 2016
Subtotal (95% CI)
Heterogeneity: Tau2 = 0.02; Chi2 = 14.23, df = 2 (P = 0.0008); I2 = 86%Test for overall effect: Z = 2.47 (P = 0.01)
Heterogeneity: Tau2 = 0.03; Chi2 = 9.77, df = 3 (P = 0.02); I2 = 69%Test for overall effect: Z = 1.41 (P = 0.16)
Heterogeneity: Tau2 = 0.00; Chi2 = 1.14, df = 2 (P = 0.57); I2 = 0%Test for overall effect: Z = 0.75 (P = 0.45)
Courneya 2014
Kamada 2017
Dankel 2016
Grøntved 2012Kamada 2017
Dankel 2016
Subtotal (95% CI)
Subtotal (95% CI)
Heterogeneity: Tau2 = 0.02; Chi2 = 37.80, df = 9 (P < 0.0001); I2 = 76%Test for overall effect: Z = 2.21 (P = 0.03)Test for subgroup differences: Chi2 = 5.90, df = 2 (P = 0.05); I2 = 66.1%
Schoenborn 2011-ASchoenborn 2011-BZhao 2014
Total (95% CI)
Heterogeneity: Tau2 = 0.00; Chi2 = 0.47, df = 2 (P = 0.79); I2 = 0%Test for overall effect: Z = 0.06 (P = 0.95)
Courneya 2014
Schoenborn 2011-ASchoenborn 2011-B
Kamada 2017Loprinzi 2015
Total (95% CI)
Heterogeneity: Tau2 = 0.02; Chi2 = 8.83, df = 4 (P = 0.07); I2 = 55%Test for overall effect: Z = 5.26 (P < 0.00001)
–0.5108 0.5119 1.8% 0.60 [0.22, 1.64]0.67 [0.45, 1.00]0.74 [0.51, 1.07]0.75 [0.69, 0.82]0.77 [0.60, 0.99]0.92 [0.87, 0.97]
8.9%9.8%
30.6%16.2%32.6%
0.20310.18990.04250.12730.0283
–0.4005–0.3011–0.2877–0.2614–0.0874
0.79 [0.69, 0.91]100.0%
–0.3285
–0.3285–0.1278
0.368 2.3%17.9%16.9%37.1%
0.04440.0298
0.72 [0.35, 1.48]0.88 [0.83, 0.93]0.72 [0.66, 0.79]0.79 [0.66, 0.95]
–0.5108 0.51190.1353
0.09680.057
–0.3147
–0.21070.0392
1.3%9.5%
15.9%12.5%39.2%
0.60 [0.22, 1.64]0.73 [0.56, 0.95]
0.81 [0.67, 0.98]1.04 [0.93, 1.16]
0.86 [0.69, 1.06]
5.3%11.6%6.8%
23.7%
–0.1508
0.09530.1044
0.1820.107
0.2189 0.86 [0.56, 1.32]
1.10 [0.77, 1.57]1.11 [0.90, 1.37]
1.07 [0.90, 1.26]
85.6%8.4%6.0% 0.87 [0.56, 1.35]
1.06 [0.73, 1.54]1.00 [0.89, 1.12]
–0.13930.0583
0.05950.19030.2248
0
100.0% 1.00 [0.89, 1.11]
100.0% 0.88 [0.78, 0.98]
5.6% 0.61 [0.28, 1.29]0.63 [0.46, 0.86]0.35 [0.17, 0.72]0.54 [0.48, 0.61]0.73 [0.60, 0.89]
20.2%6.1%
37.9%30.2%
–0.5014 0.38640.16050.36840.06010.1001
–0.462–1.0498–0.6162–0.3147
0.60 [0.49, 0.72]100.0%
2.1.3 2–5 resistance vs no-exercise
2.1.2 > 0–2 resistance vs no-exercise
2.1.4 ≥ 5 sessions of resistance vs no-exercise
Study or subgroup log[Hazard ratio] SE Weight IV, random, 95% CIHazard ratio
IV, random, 95% CIHazard ratio
Study or subgroup log[Hazard ratio] SE Weight IV, random, 95% CIHazard ratio
IV, random, 95% CIHazard ratio
Study or subgroup log[Hazard ratio] SE Weight IV, random, 95% CIHazard ratio
IV, random, 95% CIHazard ratio
Study or subgroup
(a)
(b)
(c)
(d)
log[Hazard ratio] SE Weight IV, random, 95% CIHazard ratio
IV, random, 95% CIHazard ratio
0.1 0.2 0.5 1 2 5 10Resistance No exercise
0.2 0.5 1 2 5Resistance No exercise
0.01 0.1 1 10 100Resistance ≥ 2/W Resistance <2/W
0.01 0.1 1 10 100Resistance + aerobic No exercise
Figure 2. Meta-analysis of the association between resistance training and all-cause mortality. (a) The association between� 1
sessions of resistance training in the last 30 days versus performing no exercise and all-cause mortality. (b) Subgroup analysis based on
the association between different doses of resistance training and all-cause mortality. (c) Difference between the association of �2 and
<2 sessions of resistance training per week with all-cause mortality. (d) The association of the combination of resistance training and
aerobic exercise versus no-exercise with all-cause mortality. Squares show the weight given to each study in the analysis; larger
squares represent bigger weights. Diamonds denote pooled effect size. Vertical lines represent no effect.
SE: standard error; IV: inverse variance; CI: confidence interval
Saeidifard et al. 13
Grøntved 2012
Loprinzi 2015Kamada 2017
Dankel 2016
(a)
(b)
(c)
(b)
Grøntved 2012Kamada 2017
Dankel 2016
Total (95% CI)
Total (95% CI)
Total (95% CI)
Total (95% CI)
Subtotal (95% CI)
Grøntved 2012Kamada 2017
Dankel 2016
Subtotal (95% CI)
Kraschnewski 2016Zhao 2014
Heterogeneity: Tau2 = 0.02; Chi2 = 6.20, df = 3 (P = 0.10); I2 = 52%Test for overall effect: Z = 1.83 (P = 0.07)
Heterogeneity: Tau2 = 0.05; Chi2 = 7.44, df = 2 (P = 0.02); I2 = 73%Test for overall effect: Z = 0.97 (P = 0.33)
Heterogeneity: Tau2 = 0.02; Chi2 = 2.79, df = 2 (P = 0.25); I2 = 28%Test for overall effect: Z = 1.03 (P = 0.30)
Heterogeneity: Tau2 = 0.02; Chi2 = 10.71, df = 5 (P = 0.06); I2 = 53%Test for overall effect: Z = 1.84 (P = 0.07)
Heterogeneity: Tau2 = 0.00; Chi2 = 0.28, df = 1 (P = 0.60); I2 = 0%Test for overall effect: Z = 1.55 (P = 0.12)
Heterogeneity: Tau2 = 0.06; Chi2 = 1.94, df = 1 (P = 0.16); I2 = 49%Test for overall effect: Z = 3.46 (P = 0.0005)
Test for subgroup differences: Chi2 = 0.02, df = 1 (P = 0.89); I2 = 0%
2.2.2 ≥ 2 resistance vs no-exercise
Loprinzi 2015Kamada 2017
Study or subgroup log[Hazard ratio] SE Weight IV, random, 95% CIHazard ratio
IV, Random, 95% CIHazard ratio
Study or subgroup log[Hazard ratio] SE Weight IV, random, 95% CIHazard ratio
IV, random, 95% CIHazard ratio
Study or subgroup log[Hazard ratio] SE Weight IV, random, 95% CIHazard ratio
IV, random, 95% CIHazard ratio
Study or subgroup log[Hazard ratio] SE Weight IV, random, 95% CIHazard ratio
IV, Random, 95% CIHazard ratio
–0.1199
0.6471 0.50490.06010.1339
–0.1054–0.4308
–0.4005
–0.1278
–0.5621–1.0498
0.27650.2142
0.07820.2277
89.4%10.6%
43.6%56.4%
100.0%
100.0%
0.88 [0.75, 1.03]
0.57 [0.33, 0.98]0.35 [0.23, 0.53]
0.43 [0.27, 0.70]
1.00 [0.64, 1.56]
0.89 [0.77, 1.03]
0
0.27610.1013
0.275–0.32850
0.40630.04690.12160.2244
5.7%48.4%30.7%15.1%
3.0%33.0%21.0%56.9%
8.5%
8.5%26.1%
43.1%
100.0%
100.0%
0.89 [0.40,1.97]0.91 [0.83,1.00]0.66 [0.52,0.84]0.95 [0.61,1.47]
1.91 [0.71, 5.14]0.90 [0.80, 1.01]0.65 [0.50, 0.85]0.85 [0.61, 1.19]
0.67 [0.39, 1.15]1.00 [0.82, 1.22]0.72 [0.42, 1.23]0.87 [0.67, 1.13]
0.85 [0.71, 1.01]
0.83 [0.68,1.01]
–0.0943–0.4155–0.0545
0.01 0.1 1 10 100Resistance + aerobic No exercise
0.01 0.1 1 10 100Resistance No exercise
0.05 0.2 1 5 20Resistance No exercise
0.01 0.1 1 10 100Resistance ≥2 Resistance <2
2.2.1 >0–2 sessions of resistance vs no-exercise
Figure 3. Meta-analysis of the association between resistance training and cardiovascular mortality. (a) The association between� 1
sessions of resistance training in the last 30 days versus performing no exercise and cardiovascular mortality. (b) Subgroup analysis
based on the association between different doses of resistance training and cardiovascular mortality. (c) Difference between the
association of �2 and <2 sessions of resistance training per week with cardiovascular mortality. (d) The association of the com-
bination of resistance training and aerobic exercise versus no exercise with cardiovascular mortality. Squares show the weight given to
each study in the analysis; larger squares represent bigger weights. Diamonds denote pooled effect size. Vertical lines represent no
effect.
SE: standard error; IV: inverse variance; CI: confidence interval
14 European Journal of Preventive Cardiology 0(00)
least partially explain the lower mortality in people per-forming resistance training. In addition, resistancetraining increases clearance of very low-density lipopro-tein-triglycerides from plasma as well as lipoproteinlipase gene expression and activity on the muscle cellmembranes, thereby increasing the catabolism andhydrolysis of very low-density lipoprotein-triglycer-ides.5 Lastly, resistance training improves mitochon-drial function in skeletal muscles and increases theexpression of glucose transporter type 4, the transloca-tor of glucose in the skeletal muscle, thus ultimatelyincreasing glucose uptake and glycogen synthesis inthis tissue. The overall outcome is decreased blood glu-cose and reduced cellular content of lipids, leading toimproved control of T2DM.5 The simultaneousincrease in lean mass due to resistance training alsoincreases basal metabolic rate,32 potentially contribut-ing to the prevention of obesity.
Evidence shows that performing four months ofresistance training or aerobic exercise leads to compar-able decreases in hepatic fat content, body fat mass,HBA1c levels, T2DM and non-alcoholic fatty liver
disease, while also increasing insulin sensitivity.33
In addition, a meta-analysis revealed that resistancetraining (dynamic or isometric) may significantlylower systolic and diastolic blood pressure.4 Alsoanother meta-analysis showed that resistance trainingincreases the lower and upper body strength and aer-obic fitness to a similar degree of aerobic exercise inpatients with coronary artery disease.7 All these physio-logic adaptations resulting from resistance training maylikely explain the inverse association between resistancetraining and mortality. On the other hand, Werneret al. found that, in contrast to endurance training,resistance training was not associated with telomeraseactivity and length, suggesting that resistance traininghad no anti-aging effect.34 This may explain why thepotentially beneficial effects of resistance training insurvival were modest when compared with endurancetraining.
In contrast to the improvements in overall mortalityand possible reduction in cardiovascular mortality, thisanalysis showed no significant association betweenresistance training and cancer mortality. Regardless of
Courneya 2014
Study or subgroup log[Hazard ratio] SE WeightHazard ratio
IV, random, 95% CIHazard ratio
IV, random, 95% CI
–0.6931
0.01 0.1 1 10 100Resistance
04756 15.5%84.5%
0.50 [0.20, 1.27]0.88 [0.75, 1.02]
0.81 [0.54, 1.20]
0.0748
100.0%
–0.1278Kamada 2017
Total (95% CI)
Heterogeneity: Tau2 = 0.04 ; Chi2 = 1.38, df = 1 (P = 0.24); l2 = 27%Test for overall effect: Z = 1.05 (P = 0.29)
No exercise
Dankel 2017
Study or subgroup log[Hazard ratio] SE WeightHazard ratio
IV, random, 95% CIHazard ratio
IV, random, 95% CI
0.01 0.1 1 10 100Resistance ≥2 Resistance <2
0.86 [0.72, 1.04]100.0%
–0.0834 0.3592 6.7%93.3%
0.92 [0.46, 1.86]0.86 [0.71, 1.04]0.0964–0.1508Kraschnewski 2016
Total (95% CI)
Heterogeneity: Tau2 = 0.00 ; Chi2 = 0.03, df = 1 (P = 0.86); l2 = 0%Test for overall effect: Z = 1.57 (P = 0.12)
Courneya 2014
Study or subgroup log[Hazard ratio] SE WeightHazard ratio
IV, random, 95% CIHazard ratio
IV, random, 95% CI
0.01 0.1 1 10 100Resistance + aerobic No exercise
0.90 [0.75, 1.08]100.0%
–0.4943 0.3973 5.4%94.6%
0.61 [0.28, 1.33]0.92 [0.78, 1.09]0.0842–0.0834Kamada 2017
Total (95% CI)
Heterogeneity: Tau2 = 0.00 ; Chi2 = 1.02, df = 1 (P = 0.31); l2 = 2%Test for overall effect: Z = 1.14 (P = 0.25)
(a)
(b)
(c)
Figure 4. Meta-analysis of the association between resistance training and cancer mortality. (a) The association between� 1 ses-
sions of resistance training per week versus performing no exercise and cancer mortality. (b) Difference between the association of
�2 and <2 sessions of resistance training per week with cancer mortality. (c) The association of the combination of resistance training
and aerobic exercise versus no-exercise with cancer mortality. Squares show the weight given to each study in the analysis; larger
squares represent bigger weights. Diamonds denote pooled effect size. Vertical lines represent no effect.
SE: standard error; IV: inverse variance; CI: confidence interval
Saeidifard et al. 15
its association with mortality, resistance training islikely to be particularly important for cancer patients,as it helps to improve their muscle strength and specif-ically retains lean body mass.35,36 This may help to pro-tect patients from the adverse musculoskeletal effects ofcancer treatments such as chemotherapy, as well asincreasing quality of life and functional capacity com-pared with patients that do not participate in resistancetraining.21,37,38
Besides the overall association between resistancetraining and cardiovascular outcomes, a key questionin the association between resistance training and car-diovascular outcomes is how much resistance training isassociated with maximal health benefits. The results ofthis study suggested a ‘‘U-shape’’ dose–response rela-tionship between resistance training and all-cause andcardiovascular mortality, which reflects the results ofsome of the included studies.16,23 Similarly, studies test-ing the association of resistance training with glycemiccontrol in T2DM patients showed a non-linear rela-tionship between repetition and intensity of resistancetraining and HbA1c levels.39,40 One potential explan-ation for the non-linear association between resistancetraining and mortality could be related to the possibleadverse effects of high-intensity resistance training,which may significantly affect heart rate, increaseblood pressure and lead to adverse events.41,42 Alsohigh-intensity resistance training has been associatedwith increased arterial stiffness via increasing sympa-thetic nervous system activity which contributes tochronic restraint on the arterial wall.43 The accentuatedValsalva maneuver occurring during resistance trainingmay result in some changes to heart rhythm such asbradycardia or atrial ectopy: a rapid fall in blood pres-sure after maximum workload can cause syncope evenin healthy adults.44 Finally, people performing a highvolume of resistance training may be more likely to useanabolic–androgenic steroids or supplements with sub-stances that could adversely affect their health.45 Someof our analysis suggest that the optimal health benefitsof resistance training are most likely obtained by 1–2sessions per week and avoiding high-intensity low-repe-tition type activities. However, it is important to recog-nize that the current evidence is not enough to concludethat the relationship between resistance training andsurvival has a U-shape curve.
As expected, the association between the combin-ation of the resistance and aerobic training withall-cause and cardiovascular mortality was greaterthan the association of each kind of exercises alonewith all-cause mortality. This confirms the results ofthe individual studies in this regard.14,15,21,23
To the best of our knowledge, this is the first system-atic review and meta-analysis assessing the associationbetween resistance training and total mortality and
major cardiovascular outcomes, with over 370,000participants and around nine years of follow-up.Additionally, the included studies evaluated the associ-ation exclusively between resistance training and mor-tality, adjusting for different types of exercise andfor cardiovascular risk factors, thereby increasing thevalidity of the results. This study also pooled data onthe association between the combination of resistancetraining and aerobic exercise with mortality fromdifferent causes; although the direction of the resultwas not surprising, it can be used as objective evidencesupporting current guidelines.46
This study had several limitations. Most of theincluded studies were observational studies and theonly included randomized clinical trial was on patientswith breast cancer. The observational nature of most ofthe studies is a major limitation, a limitation sharedwith the level of evidence testing the effect of aerobicexercise on major cardiovascular outcomes and mortal-ity. This raises concerns about potential confoundersnot accounted for in the multivariate analyses of eachstudy. It is possible that unaccounted confounders suchdiet, medical conditions, use of medications or anabolicsteroids may have affected the results. Most partici-pants in the primary studies represented the generalpopulation and therefore the generalizability of theresults to cardiac patients could be questionable.Studies performed in cardiac patients are needed toprove the safety and benefit of resistance trainingamong those with cardiovascular diseases. The defin-ition of resistance training between studies was hetero-geneous, underscoring the complexity of measuringresistance training dose according to type of resistancetraining, repetition, intensity, resting time and whethermachines, free weights or no equipment were used. Theexposure to resistance training was self-reported andmeasured using questionnaires. Resistance trainingwas assessed at a single time, with no informationabout initiation or changes in frequency or durationof resistance training over time, limiting the validityof the data. Furthermore, heterogeneity was high insome analyses, likely reflecting differences in the typeof resistance training or in the populations studied.Unfortunately, the differences in type and dose ofresistance training across studies could not be accur-ately determined, preventing a subgroup analysis toprove this hypothesis. There was no study that directlycompared resistance training with aerobic exercise andtheir association with mortality from different causes,limiting our ability to make conclusions about the bene-fit of performing resistance training instead of aerobicexercise. The results also highlight the limited dataassessing the association between resistance trainingand non-fatal cardiovascular outcomes such as MI,sudden death, and stroke. It also remains unclear how
16 European Journal of Preventive Cardiology 0(00)
resistance training and aerobic exercise compare, andwhat is the optimal dose of resistance training, aloneand in combination with aerobic exercise, for healthbenefits in both the general population and specificpatient groups. The limited number of eligible studieswas also a limitation, although the number of the studyparticipants was considerably large. Further studiestesting the association between resistance training andmajor cardiovascular outcomes will help to elucidatethe role of resistance training in cardiovascular diseaseprevention as well as the optimal dose and modality ofresistance training to yield any benefit.
Conclusion
There is a significant association between resistancetraining and lower all-cause mortality and a borderlineassociation with cardiovascular mortality. There areinsufficient data to determine the potential beneficialeffect of resistance training on non-fatal events or theeffect of substituting aerobic exercise with resistancetraining.
Author contribution
FS, JRMI, CPW, TPO, VKS, ARB, LJP, MV and FLJ con-
tributed to the conception or design of the work. FS and FLJcontributed to the acquisition, analysis, and interpretation ofdata, JRMI contributed to the acquisition and analysis,
CPW, TPO, VKS and ARB contributed to the interpretationand LJP contributed to the acquisition of the data for thework. FS, JRMI, CPW, TPO, VKS, ARB, LJP, MV and
FLJ drafted the manuscript. FS, JRMI, CPW, TPO, VKS,ARB, LJP, MV and FLJ critically revised the manuscript. Allgave final approval and agree to be accountable for all aspects
of work ensuring integrity and accuracy.
Acknowledgements
We thank Dr. Paul D Loprinzi, Associate Professor of theUniversity of Mississippi, Dr. Frank B Hu, Professor of
Harvard T.H. Chan School of Public Health, and Dr.Anders Grøntved, Associate Professor of University ofSouthern Denmark, for providing additional data, and alsoDr. Lucy Robinson from InsightEditingLondon for editing
the manuscript.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest withrespect to the research, authorship, and/or publication of this
article.
Funding
The author(s) disclosed receipt of the following financial sup-port for the research, authorship, and/or publication of this
article: This work was supported by the Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123), by project no. LQ1605from the National Program of Sustainability II (MEYS CR),
by the project ICRC-ERA-Human Bridge (No. 316345),funded by the 7th Framework Program of the EuropeanUnion, NIH/NHLBI grant (No. HL-126638 to TPO) and
National Institute of Health (NIH) grants (R01HL-134808and R01HL-114024 to V.K.S). The content is solely theresponsibility of the authors and does not necessarily repre-sent the official views of the NIH.
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