Advance Publication by-J-STAGE

Circulation Journal
Official Journal of the Japanese Circulation Society
REVIEW
http://www. j-circ.or.jp

Physical Activity, Cardiorespiratory Fitness,

and Exercise Training in Primary and
Secondary Coronary Prevention
Damon L. Swift, PhD; Carl J. Lavie, MD; Neil M. Johannsen, PhD; Ross Arena, PhD;
Conrad P. Earnest, PhD; James H. O’Keefe, MD; Richard V. Milani, MD;
Steven N. Blair, PED; Timothy S. Church, MD, PhD

Substantial data have established that higher levels of physical activity (PA), participating in exercise training (ET),
and higher overall cardiorespiratory fitness (CRF) provide considerable protection in the primary and secondary
prevention of coronary heart disease (CHD). This review surveys data from epidemiological and prospective ET
studies supporting the favorable impact of PA, ET, and CRF in primary CHD prevention. Clearly, cardiac rehabilita-
tion and ET (CRET) programs have been underutilized for patients with CHD, particularly considering the effect of
CRET on CHD risk factors, including CRF, obesity indices, fat distribution, plasma lipids, inflammation, and psycho-
logical distress, as well as overall morbidity and mortality. These data strongly support the routine referral of patients
with CHD to CRET programs and that patients should be vigorously encouraged to attend CRET following major
CHD events.

Key Words: Cardiac rehabilitation; Coronary heart disease; Exercise; Fitness

T
he American Heart Association has established that a
sedentary lifestyle is a major modifiable risk factor for
coronary heart disease (CHD).1 Nevertheless, a siz-
able percentage of the United States’ population is sedentary or
at least relatively inactive. Based on substantial data, many
health organizations have recommended increased physical
activity (PA) and exercise training (ET) to increase cardiore-
spiratory fitness (CRF), which are reviewed in the current joint
positions from the American College of Sports Medicine
(ACSM)2 and the 2008 Federal Physical Activity Guidelines.3
In this review, we discuss the interaction of PA, obesity, and
CRF on overall cardiovascular (CV) risk, including the effect
of occupational PA and ET studies. Also, the role of formal
cardiac rehabilitation and ET (CRET) secondary prevention
programs on CHD risk factors and major CHD morbidity and
mortality in secondary prevention of CHD are reviewed.
PA Levels and CV Risk
Epidemiological data demonstrate that low levels of PA are
associated with a higher prevalence of hypertension (HTN),4–6
obesity,7,8 type 2 diabetes mellitus (T2DM)9–11 and metabolic
syndrome (MetSyn).12–14 Similarly, ample published data dem-
onstrate a strong inverse association between PA levels and
CV mortality.15–20 In the Whitehall study (n=6,702), Smith et al
observed a 38% reduction in CV mortality (not including CHD)
with high levels of leisure-time PA compared to low levels in
men who were London civil servants.21 Sesso et al22 in the
Harvard Alumni study (n=12,516) observed a significant trend
for lower CHD risk in middle-aged and older men with highest
tertile (≥12,600 KJ/week, relative risk: 0.73) of PA levels com-
pared to those in the lowest tertile (<2,100 KJ/week, referent).
Additionally, men with PA levels greater than 4,200 KJ/week
(consistent with 30 min of PA on most days of the week) or
higher had approximately 19–20% reduction in CHD risk.
In the Women’s Health Study (n=39,372), Lee et al23 ob-
served that higher levels of energy expenditure were associ-
ated with a lower relative risk of CHD in middle-aged and
older women. In addition, walking at least 1.0 h or more per
week was associated with >50% reduction in CHD risk in

Received January 6, 2013; accepted January 7, 2013; released online January 18, 2013
Department of Preventive Medicine, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA (D.
L.S., C.J.L., N.M.J., C.P.E., T.S.C.); Department of Cardiovascular Diseases, Ochsner Clinical School, The University of Queensland
School of Medicine, New Orleans, LA (C.J.L., R.V.M.); Division of Physical Therapy, Department of Orthopedics and Rehabilitation
and Division of Cardiology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM (R.A.);
Department of Health, University of Bath, Bath (C.P.E.), United Kingdom; Mid America Heart Institute, St. Luke’s Hospital of Kansas
City, MO (J.H.O.); and Departments of Exercise Science and Epidemiology/Biostatistics, University of South Carolina, Columbia, SC
(S.N.B.), USA
Mailing address:  Carl J. Lavie, MD, FACC, FACP, FCCP, Medical Director, Cardiac Rehabilitation and Preventive Cardiology, John
Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, 1514 Jefferson
Highway, New Orleans, LA 70121-2483, USA.   E-mail: clavie@ochsner.org
ISSN-1346-9843   doi: 10.1253/circj.CJ-13-0007
All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp
 Advance Publication by-J-STAGE
multivariate models. Li et al observed that women in the
Nurse’s Health Study (n=88,393) who were moderately active
(1–3.49 h/week) and active (≥3.5 h/week), had 43% and 58%
lower risk of CHD, respectively, compared to sedentary women
(<1 h/week).24 Hu et al18 in their study of Finish participants
(n=47,840) observed that a high level of leisure-time PA was
associated with 16% and 23% reductions in CHD risk for men
and women, respectively, compared to those with low levels of
PA. A recent meta-analysis by Li and Siegrist25 observed that
in men, moderate and high levels of leisure-time PA had 20%
and 24% reductions in CHD risk, respectively. In women, they
were associated with 18% and 27% reductions in CHD risk,
respectively. Similarly, a meta-analysis by Sofi et al observed
that moderate and high levels of PA were associated with 12%
and 27% reductions in CHD incidence, respectively.26
High levels of PA have also been shown to reduce CV mor-
tality in higher risk populations, such as individuals with
T2DM and the elderly. Hu et al observed 16% and 31% reduc-
tions in CV mortality (n=3,316) with moderate and high levels,
respectively, of leisure-time PA in Finish adults with T2DM.17
In the Zutphen Elderly Study (n=802), Bijnen et al27 observed
a significant trend for lower 10-year CV mortality (15%), but
not CHD mortality, with higher levels of PA in elderly Dutch
men (age: 64–84 years). In the same study, men classified as
active (20 min of exercise at least 3 times per week) had a 34%
reduction in 10-year CV mortality compared to men classified
as inactive. Thus, the available evidence strongly suggests an
inverse association exists between PA level and CV mortality
and CHD risk.
Interactions Among Obesity, PA and CV Risk
Several studies have evaluated the potential interaction be-
tween PA level and obesity on CV mortality risk. The consen-
sus among studies is that higher levels of PA attenuate, but do
not completely eliminate, the elevated CV mortality risk as-
sociated with obesity. Hu et al16 in the Nurses’ Health Study
(n=116,564) observed that the relative risk of CV mortality
was markedly reduced in obese women with higher levels
of PA compared to those with lower levels. However, obese
women still had elevated risk compared to normal-weight
(body mass index [BMI] <25 kg/m2) women with high levels
of PA. Similarly, Fang et al,28 using National Health and Nutri-
tion Examination Survey data (n=9,790), observed using Cox
regression analyses that obese individuals (BMI >30 kg/m2,
hazard ratio: 1.24) and those in the lowest tertile of PA (hazard
ratio: 1.32) were at an elevated risk of CV mortality even after
multivariable adjustments. Weinstein et al in the Women’s
Health Study (n=38,987) observed that active overweight
(hazard ratio: 1.5) and obese (hazard ratio: 1.87) women had
elevated CHD risk compared to normal-weight individuals.29
A limitation of all these studies is that PA was assessed by
self-report questionnaires, which are quite inaccurate and lead
to substantial misclassification. This likely means that these
studies potentially do not adequately adjust for PA when eval-
uating the effects of obesity on health outcomes.
Changes in PA Level and CV Risk
The available evidence from epidemiologic studies suggests
that increasing the level of PA is associated with reductions in
CV mortality and CHD risk. Paffenbarger et al30 in the Har-
vard Alumni Study (n=10,269) observed that sedentary indi-
viduals who increased the amount of moderate to vigorous PA
had a 41% lower risk of CHD compared to those who re-
mained sedentary. However, increasing PA levels (defined as
SWIFT DL et al.
an increase in 2,000 kcal/week determined through question-
naire) were not associated with a reduction in all-cause mortal-
ity or CHD risk. In older women (n=7,553, median follow-up:
5.7 years), Gregg et al observed that increasing the level of
PA, based on the Harvard Alumni Questionnaire, was associ-
ated with a 36% reduction in CV mortality in sedentary older
women.31 Lastly, Wannemethee et al observed that in middle-
aged British men (n=5,936, 4 years follow-up) increasing the
level of PA from inactive to at least lightly active was associ-
ated with a 45% reduction in CV mortality compared to those
that were inactive at both examinations.32
Occupational PA and CV Risk
Several studies have explored PA and CV risk in occupa-
tional settings, with much of the available data from Finish
cohorts. Slattery et al20 observed that male US railroad work-
ers (n=3,043) who were sedentary (expended <40 kcals/week)
based on PA questionnaires, had a 39% greater risk of CHD
compared to men with higher PA (3,632 kcals/week).20 Simi-
larly, Hu18 et al observed that in middle-aged Finnish men and
women (n=47,840) free of CHD or stroke at baseline, a high
level of occupational PA was associated with 10% and 20%
reductions in the risk of CHD in men and women, respectively,
after adjustment for covariates and commuting and leisure-
time PA.18 Hu et al, in a different study, observed that among
Finnish adults with T2DM (n=3,316, mean follow-up: 18.4
years) high moderate/vigorous occupational PA was indepen-
dently associated with a 31% reduction in CV mortality, even
after adjustments for age, sex, BMI, systolic blood pressure,
and commuting and leisure-time PA.17 Barengo et al, in an-
other cohort of Finnish adults (n=15,853 men and 16,824
women) observed that high levels of occupational PA were
associated with similar reductions in CV mortality in both men
and women (33%) in the fully adjusted models, which in-
cluded both commuting and leisure-time PA.15 Thus, the cur-
rent data available suggest that low levels of occupational PA
may have an independent contribution to CV mortality risk.
CRF and CV Risk
Similar to low levels of PA, a low level of CRF is a well-rec-
ognized risk factor for CV and CHD mortality. In general,
epidemiological studies define CRF as the highest level of
estimated metabolic equivalents (METs) (or in some cases
peak or maximal oxygen consumption) achieved during a max-
imal exertion treadmill test. Study participants generally exer-
cise to at least 85% of age-predicted maximum heart rate or
to volitional exhaustion.33 High levels of CRF have been as-
sociated with reduced prevalence of several CV risk factors
such as HTN34,35 and obesity36,37 and lower incidence rates of
MetSyn38–40 and T2DM.41–43
Epidemiologic data suggest an inverse association between
CRF level and CV mortality. Blair et al, in the Aerobics Center
Longitudinal Study (ACLS; n=25,341 men and 7,080 women),
observed a substantially higher relative risk of CV mortality in
men and women categorized as having low CRF even after
multivariate adjustments compared to adults with high levels
of CRF.44 Mora et al,45 in the Lipid Research Clinics Preva-
lence study (n=2,994), observed that low levels of CRF (de-
fined as ≤ median value) were associated with almost a 2-fold
increase in CV mortality risk in asymptomatic women after 20
years of follow-up. Furthermore, an estimated one MET in-
crease in CRF was associated with a 17% increased risk in CV
mortality. A recent meta-analysis by Kodama et al46 observed
that a 1 MET increase in CRF was associated with 13% and
 Advance Publication by-J-STAGE
Exercise and Coronary Prevention
15% reductions in all-cause and CVD/CHD mortality, respec-
tively. In addition, the authors defined minimum levels of CRF
associated with lower event rates in both men (40 years: 9
METs, 50 years: 8 METs, 60 years: 7 METs) and women (40
years: 7 METs, 50 years: 6 METs, 60 years: 5 METs) based
on age.
High levels of CRF are also associated with lower CV mor-
tality risk in otherwise high-risk individuals. Katzmarzyk et al,
using ACLS data, observed that in men with MetSyn (n=3,757),
a low level of CRF was associated with a 2.6-fold higher CV
mortality risk compared to men with a higher level of CRF.47
Similarly, Lyerly et al,48 also using ACLS data, observed that
in women (n=3,044) with pre-diabetes or undiagnosed T2DM,
moderate and high levels of CRF were associated with reduced
mortality by approximately 37% and 39%, respectively, com-
pared to women with low CRF.48 McAuley et al, in the Veter-
ans Exercise Testing study (n=7,775), observed that in men
with T2DM (without baseline CVD) those with high CRF had
2.5- and 3.8-fold reductions in all-cause mortality risk com-
pared to men in the moderate or low CRF categories, respec-
tively, after multivariate adjustments.49 Berry et al observed in
men in the ACLS dataset (n=11,049) that low levels of CRF
were associated with a higher lifetime risk of CV mortality to
age 80 years, with markedly lower rates at 45 (high CRF: 3.4
vs. low CRF: 12.2%), 55 (high CRF: 4.9 vs. low CRF: 19.6%)
and 65 (high CRF: 5.6 vs. low CRF: 12.2%) years old com-
pared to those with low levels of CRF.50 Especially notable
in their findings, men with a high burden of traditional CV
risk factors, but with a high level of CRF, had lifetime CV
mortality rates that were similar to those with a low burden of
traditional CVD risk factors.50 In summary, these data suggest
that increasing or maintaining a high level of CRF may be of
particular importance in individuals with known CVD risk
factors.
Independent Effects of CRF and Obesity
Several researchers have evaluated the independent effects of
CRF and obesity on CV mortality. Overwhelming evidence
exists that high levels of CRF attenuates the CV mortality risk
in overweight and obese individuals.51–55 Wei et al observed in
men in the ACLS dataset (n=25,714) that low levels of CRF
elevated the relative risk of CV mortality similarly in normal
weight (1.7), overweight (1.9) and obese men (2.0) compared
to normal-weight men without low CRF.55 Stevens et al, in the
Lipid Research Clinics Study (n=5,366), demonstrated that
men and women (RR=1.39 for both) classified as fat and fit
did not have a significantly higher relative risk of CV mortal-
ity compared to the reference group who were both fit and
lean, although the relationship for men did approach signifi-
cance (P<0.06).53 Lee et al, using the ACLS dataset (n=21,925),
evaluated this relationship using body fat (≥25.0%) as a mea-
sure of obesity and observed that the relative risk of CV mor-
tality was substantially lower in men who were obese and fit
(1.35) compared to men who were obese and unfit (4.08), but
not significantly different from the reference group (men who
were lean and fit).56 Church et al, studying men with T2DM in
the ACLS dataset, observed a significant reduction in the rela-
tive risk of CV disease mortality in normal weight (low: 2.7,
high: 1.0) and obese individuals (low: 2.7, moderate/high: 1.5)
with T2DM and a trend for similar effects in individuals clas-
sified as overweight (low: 2.7, high: 1.5, P-trend=0.07).51
Thus, the available epidemiological evidence suggests that a
high level of CRF is associated with markedly reduced CV
mortality risk, regardless of BMI or adiposity.
Importantly, most of the available data suggest that even in
lean and normal-weight individuals, CV mortality is increased
with low levels of CRF. Lee et al observed an approximately
3-fold increase in CV mortality in lean men who were unfit
compared to lean, fit men.56 Similarly, Stevens et al observed
>50% increase in CV mortality in men categorized as unfit/not
fat compared to fit/not fat men.53
Changes in CRF and CV Risk
The few studies that have evaluated the effect of a change in
CRF on CV mortality endpoints have observed that improving
the level of CRF generally has a protective effect on CV mortal-
ity. The best-known study in this area was conducted by Blair
et al, using ACLS data (n=9,777), in which they showed that
men classified as unfit at the first examination and fit at the
second examination had a 52% reduction in CV mortality com-
pared to men who were unfit at both examinations.57 Erikssen
et al58 observed that among middle-aged men (n=2,014), there
was an inverse association between the change in CRF (de-
fined as the ratio of the maximum cycle ergometer workload
of the 2nd examination divided by the 1st examination) and CV
mortality (50% and 53% reductions in risk in the 2 highest
quartiles compared to the lowest quartile).58 Lee et al,59 using
the ACLS dataset (n=14,345), evaluated the long-term effects
of a change in CRF on CV mortality (mean follow-up, 11.4
years) and observed a significant reduction in CV mortality in
men who had either no change (27%) or increased CRF (42%)
at the second examination separated by 6.3 years that persisted
even after adjustments for change in BMI. Furthermore, for
every 1 MET increase in CRF over time, there were 15% and
19% reductions in all-cause and CV mortality, respectively.
Although cause and effect relationships cannot be determined
based on these epidemiological studies and similar data con-
firming these relationships in women are needed, the studies
presented provide strong evidence that improving the level of
CRF has a favorable effect on CV mortality.
Is PA or CRF Level the Best Predictor
of CV Mortality?
Some studies have compared the relative importance of the
CRF and PA levels on CV mortality. The available data in this
area suggests that CRF is the more clinically important predic-
tor of CV and mortality outcomes60,61 after controlling for CV
risk factors.62 However, it is important to consider (as stated in
a recent review article by Blair et al63) that much of the epide-
miological data evaluating PA and CVD risk has been deter-
mined through self-report questionnaires whereas high CRF,
after accounting for genetic heritability (which is extremely
important),64 is primarily determined by regular PA. Simply
stated, CRF may be a better measure of habitual PA than are
responses to self-report questionnaires.
Public Health Recommendations for PA
Increasing the amount of PA or ET is recommended by a va-
riety of health organizations3,65–67 to reduce the risk of CV
disease in sedentary adults, because of the favorable effects of
exercise on CRF and other CVD risk factors. The current joint
position stand from the ACSM2 and the 2008 Federal Physical
Activity Guidelines3 recommend that adults obtain at least
150 min of moderate-intensity PA per week or 75 min of vig-
orous-intensity PA per week, and specifically state that all
adults should avoid inactivity. For individuals who are unable
to attain the current recommendations for PA, some PA likely
has health benefits over remaining sedentary.2,3,67 The Guide-
 Advance Publication by-J-STAGE
lines also set a higher recommendation of 300 min of moder-
ate-intensity activity per week or 150 min of vigorous activity
per week to obtain even greater health benefits. The Guidelines
also indicate that a person can combine moderate and vigorous
intensity to reach the recommendations, with 1 min of vigor-
ous being equal to 2 min of moderate. Thus, 25 min of vigorous
intensity (2×25) combined with 100 min of moderate intensity
would meet the basic recommendation of 150 min/week.
ET and CRF
As mentioned earlier in this review, CRF is important for pre-
dicting CV mortality. Aerobic ET of sufficient intensity and
volume has well-established effects on improving CRF. The
ACSM recommends moderate or vigorous aerobic ET in order
to maintain or increase CRF.2,66 Evidence from large random-
ized controlled trials supports that increases in CRF can be
achieved with moderate-intensity aerobic ET programs. Kraus
et al, in the Studies of Targeted Risk Reduction Interventions
through Defined Exercise (STRRIDE, n=111), observed a
significant increase in CRF level following 8 months of mod-
erate-intensity (45–55% V̇O2max) aerobic ET in sedentary
overweight men and women.68 Church et al, in the Dose Re-
sponse to Exercise in Women (DREW, n=464) study, observed
significant increases in CRF in postmenopausal women fol-
lowing 6 months of moderate-intensity cycle ergometer ET
(50% V̇O2max), and a greater improvement in CRF with a
greater amount of ET.69 Thus, for sedentary adults, moderate-
intensity ET is likely a sufficient stimulus to improve CRF.
In terms of the effect of aerobic ET intensity on CRF, the
prevailing view is that larger gains in CRF may be obtained
with higher intensity aerobic ET (training at a higher percent-
age of maximal CRF levels).2 Crouse et al observed a greater
increase in CRF in men exercising at high intensity as opposed
to moderate intensity (measured via peak V̇O2) in middle-aged
men (n=26) following 24 weeks of cycle ergometer exercise.70
Similarly, O’Donovan et al observed a greater increase in CRF
following 24 weeks of high-intensity ET in sedentary men
(n=64) compared to moderate-intensity ET matched for ET
energy costs.71 In addition, several studies suggest that high-
intensity aerobic ET is associated with greater responses in
glucose control,72 insulin sensitivity,73,74 and visceral fat loss75
compared to moderate-intensity ET.
Thus, the available evidence suggests that vigorous ET con-
fers equal or enhanced health benefits when compared to mod-
erate ET when matched for total caloric expenditure.76 In ad-
dition, when moderate- and vigorous-intensity aerobic ET are
matched for total exercise time, a greater caloric expenditure
is achieved with higher ET intensities,76 which has the poten-
tial to produce additional health benefits. It is important to keep
in mind that most of the studies in this area have small sample
sizes with varying methodologies/study populations, and have
had mixed results. Therefore, more empirical evidence from
large clinical trials is still needed to confirm and expand the
findings in regard to CRF and other CV risk factors.
Effect of ET on Traditional CV Risk Factors
Cholesterol   The most consistent effect of aerobic ET on
lipids tends to be restricted to improvements in high-density
lipoprotein-cholesterol (HDL-C). Kraus et al observed a sig-
nificant increase in HDL-C in overweight adults with high
level and high-intensity aerobic ET, but not with low levels of
aerobic ET (at either high or low intensities).77 In the same
study, Kraus et al showed that all ET groups (regardless of
amount or intensity) had beneficial changes in low-density li-
poprotein (LDL) particle size. A recent review article by Tam-
SWIFT DL et al.
balis et al reported an increase in HDL-C of approximately
9.8% in studies utilizing moderate-intensity aerobic ET.78
Similarly, Kodama et al, in a recent meta-analysis, observed
that aerobic ET resulted in an increase in HDL-C of 2.5 mg/dl,
and that both ET duration and caloric expenditure were sig-
nificantly associated with increases in HDL-C.79
Glucose Control   ET is recommended by the Joint Position
Stand by ACSM and the American Diabetes Association,65
specifically the combination of aerobic and resistance training
when feasible to maximize the improvement in glucose control
in individuals with T2DM. Both Church et al80 and Sigal et al81
observed the greatest reductions in hemoglobin A1c (HbA1c)
levels in adults with T2DM following combination ET pro-
grams (using both aerobic and resistance ET), whereas the im-
provements in HbA1c with aerobic or resistance training alone
were inconsistent in the 2 studies. The reduction in HbA1c
with ET has been associated with a reduction in both body
fat82 and central adiposity,82 and an increase in CRF,82,83 mus-
cular strength84 and ET intensity.72 It has also been reported
that ET reduces the prevalence of MetSyn. Katzmarzyk et al,
in the Heritage Family Study, observed a 32% reduction in
MetSyn prevalence following 20 weeks of aerobic ET.85
Weight and Adiposity   Weight loss solely from ET (with-
out dietary caloric restriction) is generally modest (ie, <3% of
body weight) in controlled ET studies.86 The ACSM Position
Stand on this topic notes that public health recommenda-
tions of 150 min/week of moderate PA have generally not
shown clinically significant weight loss, and have the potential
for modest absolute weight loss (<2.5 kg).86 In addition, adop-
tion of PA levels below those recommended is unlikely to
produce clinically significant weight loss.86 Church et al, in
the DREW study (n=464), observed no significant changes in
body weight in postmenopausal women exercising at low-to-
moderate-intensity levels consistent with public health rec-
ommendations (−2.2 kg) or 50% above (−0.6 kg) or 50% below
those recommendations (−0.4 kg).69 Donnelly et al, in the
Midwest Exercise Trial, observed clinically significant weight
loss in men (−5.2 kg, −5.5% of baseline body weight), but not
women (0.6 kg) after 16 weeks (225 min/week) of aerobic
ET.87 Although clinically significant weight loss generally
does not occur in ET trials, other favorable cardiometabolic
changes, such as improvements in insulin sensitivity,88 waist
circumference,69,89,90 HDL-C,91 total fat,90,91 visceral fat,89–92
and interleukin-6 concentration89 have been observed follow-
ing aerobic ET without weight loss. Thus, it is important to
remember that PA is beneficial whether or not significant
weight loss occurs.
Blood Pressure   Following ET, there appears to be a ben-
eficial effect on HTN; however, the magnitude of the effects
on resting blood pressure among studies tends to be variable.93
Whelton et al, in a meta-analysis of 54 controlled trials, ob-
served that ET was associated with reductions of −3.8 and
−2.6 mmHg in systolic and diastolic blood pressure, respec-
tively.94 Similarly, a recent meta-analysis by Cornelissen et
al95 demonstrated that aerobic ET was associated with reduc-
tions of blood pressure in participants with normal blood pres-
sure (systolic: −2.4, diastolic: −1.6 mmHg), pre-HTN (systolic:
−1.7, diastolic: −1.7 mmHg), and HTN (systolic: −6.9, diastolic:
−4.9 mmHg). Based on their additional analyses, the authors
concluded that the hypotensive effects of aerobic ET may be
related to reductions in systemic vascular resistance (−7.1%),
plasma norepinephrine concentration (−28.7%) and plasma
renin activity (−19.8%).
 Advance Publication by-J-STAGE
Exercise and Coronary Prevention
ET and Secondary CHD Prevention
Those Who Think They Have No Time for Bodily Exercise
Will Sooner or Later Have to Find Time for Illness
– Earl of Derby96 –
Several observational studies, as well as randomized controlled
trials, have established the benefits of PA and ET in cohorts
with established CHD.97–99 Perhaps the best example of ET and
secondary CHD prevention comes from data collected in for-
mal CRET secondary prevention programs. A broad range of
patients, with defined clinical characteristics, benefit from for-
mal CRET programs, which is summarized in Table 1.
Effect of CRET on Exercise Capacity
Probably the most important benefit of formal CRET is the
improvement in CRF.97–99 Our studies have noted considerable
discrepancy between estimated maximal METs as determined
by peak treadmill speed and grade and maximal CRF assessed
by gas exchange (peak V̇O2).100–102 Because this terminology
is confusing, we prefer clinically to define CRF as either esti-
mated METs or measured peak V̇O2. Our studies of CHD
patients demonstrate that estimated maximal METs signifi-
cantly overestimate measured CRF, both before but, particu-
larly, following an ET program (and even more so in younger
than in older patients). Nevertheless, considerable data that
have estimated CRF (discussed earlier), as well as studies
using gas exchange, have determined that measures of CRF
are a major predictor of mortality in CHD patients.100–103 Al-
though patients with low CRF benefit more from CRET than
do patients with high CRF, we have demonstrated that even
patients with high CRF obtain marked improvements follow-
ing CRET.104 In a study of CRET for nearly 15,000 men and
women, every 1 mlO2 · kg–1 · min–1 increase in directly mea-
sured peak V̇O2 showed a nearly 10% reduction in major CV
mortality.105,106 In another study, total mortality fell by 2% for
every 1% increase in peak V̇O2 with CRET.107
Effect of CRET on Lipids and Inflammation
The overall effects of CRET on levels of LDL-cholesterol are
minimal, especially considering the current extremely high
background use of statins, more so at high doses.108–110 Many
CHD patients have dyslipidemia, including low levels of
HDL-C and/or high levels of triglycerides (TGs) that often
markedly improve following formal CRET.97–99 Typically, the
improvements in HDL-C and TG concentrations are modest
(eg, +6% and −15%, respectively) following CRET, although
greater improvements are typically observed in patients with
abnormal baseline lipid values.111–113 The Ochsner group and
others have demonstrated the significance of systemic inflam-
mation, particularly as assessed by levels of high-sensitivity
C-reactive protein (hs-CRP), in both primary and secondary
prevention.114,115 Additionally, we have reviewed the potential
improvements in hs-CRP with PA and ET, and the improve-
ment in overall CRF.116
In a study of 277 patients with stable CHD following major
CHD events, we demonstrated that hs-CRP fell by almost 40%
in 235 patients who completed formal CRET, with no improve-
ment noted in the 42 controlled patients who did not attend
CRET (Figure 1).117 We also demonstrated that CHD patients
with MetSyn had approximately 2-fold higher levels of hs-
CRP compared with CHD patients without MetSyn, but both
groups of patients had approximately 40% reductions in hs-
CRP following formal CRET programs.118 Whereas lean CHD
patients had <20% reductions in hs-CRP following CRET,
which were not statistically significant, the obese patients had
Table 1.  Benefits of Formal Cardiac Rehabilitation and
Exercise Training Programs
Improvement in exercise capacity
   1. Estimated METS +35%
   2. Peak V̇O2 +15%
   3. Peak anaerobic threshold +11%
Improvement in lipid profiles
   1. Total cholesterol –5%
   2. Triglycerides –15%
   3. HDL-C +6% (higher in patients with low baseline)
   4. LDL-C –2%
   5. LDL-C/HDL-C –5% (higher in certain subgroups)
Reduction in inflammation
     hs-CRP –40%
Reduction in indices of obesity
   1. BMI –1.5%
   2. % fat –5%
   3. Metabolic syndrome –37%
Improvements in behavioral characteristics
   1. Depression
   2. Anxiety
   3. Hostility
   4. Somatization
   5. Overall psychological distress
Improvements in quality of life and components
Improvement in autonomic tone
   1. Increased heart rate recovery
   2. Increased heart rate variability
   3. Reduced resting pulse
Improvements in blood rheology
Reduction in hospitalization costs
Reduction in major morbidity and mortality
BMI, body mass index; hs-CRP, high-sensitivity C-reactive protein;
HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density
lipoprotein-cholesterol.
nearly 45% reductions in hs-CRP following CRET.119 In a
more recent study, we assessed the relationship between hs-
CRP and weight loss with CRET, and we demonstrated that
overweight/obese individuals who had greater than median
weight loss (average reduction in weight, 5%) with CRET, also
had a 40% reduction in hs-CRP, whereas those without a sig-
nificant weight loss only had a minimal (6%) reduction in hs-
CRP (Figure 2).120 Others have reported significant improve-
ments in hs-CRP with CRET.121,122
Effect of CRET on Obesity
Considering the extremely high prevalence of overweight/obe-
sity in Western society and, particularly, in patients with CHD,
the potential important benefit of formal CRET programs is
promotion of weight reduction and weight maintenance.97–99
Although the Ochsner group and others have published exten-
sively on the obesity paradox in patients with CV diseases,
including CHD,123–135 we believe that most data still support
the benefits of purposeful weight reduction.136 Further, data
from CRET programs have established the efficacy and safety
of weight loss in patients with CHD, especially in those with
MetSyn, where a 37% reduction in the prevalence of MetSyn
has occurred following CRET.118
In a small group of 45 obese patients with CHD from our
CRET program who successfully lost weight following CRET
 Advance Publication by-J-STAGE
Figure 1.    Median changes in high-sensitivity C-reactive pro-
tein concentration in control patients with coronary heart dis-
ease (CHD) and cardiac rehabilitation patients (data adapted
from Milani RV et al117).
(>5% weight loss; mean 10%), we noted statistically greater
improvements in CRF and plasma lipids compared with 81
obese patients who did not lose weight.137 A recent study of
377 consecutive patients from the CRET program at the Mayo
Clinic demonstrated that weight loss was associated with re-
ductions in total mortality plus major CV events, and these
improvements were noted even among those CRET patients
with baseline BMI <25 kg/m2, as well as in those in the higher
BMI groups.138 Data from Ades et al demonstrated that great-
er weight loss with CRET, utilizing a high-caloric-expenditure
(3,000–3,500 kcal/week) ET program, was associated with
reduced insulin resistance, improved lipids (reductions in TGs
and increases in HDL-C), as well as reduced plasminogen
activator inhibitor I concentration and blood pressure.121 Fi-
nally, a study of more than 1,500 overweight/obese CHD pa-
tients demonstrated that intentional weight loss from dietary
therapy alone, without specific ET, produced a lower incidence
of CHD events over a 3-year follow-up compared to patients
without intentional weight loss.139 In aggregate, these studies
support the potential benefits of weight loss in CHD patients,
and that more successful weight loss with CRET results in
greater improvements in CHD risk.
Effect of CRET on Psychological Risk Factors
It Is Exercise Alone That Supports the Spirit, and Keeps
the Mind in Vigor – Cicero140 –
Perhaps some of the most important data on the effect of CRET
is in the area of psychological stress (PS), including levels of
depression, hostility, anxiety, and total PS.141 We have docu-
mented a high prevalence of PS risk factors in patients with
CHD,142–144 with marked benefits following formal CRET
programs (Figure 3).143 For example, we have demonstrated
SWIFT DL et al.
Figure 2.    Mean concentration of high-sensitivity C-reactive
protein before and after cardiac rehabilitation and exercise
training in 393 overweight and obese patients with coronary
heart disease (CHD) divided by median weight loss (data
adapted from Lavie CJ120).
that those patients with depression who completed CRET had
>70% reduction in 3-year mortality (8% vs. 30%, P<0.001)
compared with a control group of depressed CHD patients
who did not attend CRET.145 However, patients who remained
depressed had 4-fold higher 3-year mortality (P<0.001).
In order to make the link between improvements in CRF
and depression-related mortality, we divided patients into those
who achieved mild improvement in peak V̇O2 following CRET
(≤10%; n=135), those who had more marked improvements
in peak V̇O2 (>10%; n=285), and those who did not improve
CRF (n=102). We demonstrated that only a small improve-
ment in peak V̇O2 is required to produce significant reductions
in depression and depression-related increased mortality risk,
which were very similar to the improvements noted in those
who achieved more marked improvements in peak V̇O2
(Figure 4).145 Very recently, we demonstrated similar marked
improvements following CRET in depression and depression-
related mortality risk in high-risk CHD patients with systolic
heart failure.146
Similar benefits of CRET are noted in patients with high
total scores for PS,147 as well as in those with high PS-associ-
ated increased mortality risk.148
Effect of CRET on Morbidity and Mortality
Although sometimes more difficult to demonstrate, perhaps the
most important benefit of referring patients to formal CRET
after major CHD events is the marked effects on major CV
morbidity and mortality. One of the first major meta-analyses
of CRET programs by O’Connor et al149 in 1989 included 22
randomized controlled trials in 4,551 CHD patients who were
post-myocardial infarction (MI). This major meta-analysis
demonstrated reductions in total and CV mortality of 20% and
25%, respectively, at 3-year follow-up after CRET. Addition-
 Advance Publication by-J-STAGE
Exercise and Coronary Prevention

Figure 3.    Effect of formal cardiac 

rehabilitation and exercise training
programs on prevalence of adverse 
psychological stress parameters (de-
pression, anxiety, and hostility) in
younger and older patients with coro-
nary heart disease (data adapted from
Lavie and Milani143).

Figure 4.    Prevalence of depression and subsequent mortality based on changes in peak oxygen consumption (V̇O2) during cardiac
rehabilitation and exercise training. *P<0.001 compared with V̇O2 loss (data adapted from Milani and Lavie145).

ally, there was a significant 37% reduction in sudden cardiac
death after 1 year, with strong trends for reductions in sudden
cardiac death at 2- and 3-year follow-up. A more recent meta-
analysis of 8,440 participants from 32 randomized controlled
trials demonstrated a 31% reduction in CV mortality following
CRET.150 Although there have been many advances in medical
and interventional therapies that have improved prognosis fol-
lowing MI, a recent analysis of 1,821 post-MI patients from
the Mayo Clinic (Olmsted County, Minnesota residents) dem-
onstrated that the benefits of CRET were greater during the
past decade compared to several decades previously, suggest-
ing that the benefits of CRET are not decreasing over time.151
Although most of the CRET benefits have been described in
post-MI patients, these benefits have recently been assessed by
Goel et al152 utilizing Olmsted County, Minnesota Registry
data from patients following percutaneous coronary interven-
tion (PCI). In 2,395 consecutive post-PCI patients, participa-
tion in formal CRET was associated with a 45% reduction
(P<0.001) in all-cause mortality during a 6-year follow-up,
with a strong trend for a reduction in CV mortality among
those who participated in CRET, with the benefits of CRET
seen regardless of type of PCI (elective or urgent), sex, and age.
 Advance Publication by-J-STAGE
SWIFT DL et al.

Table 2.  Exercise Prescription in Primary and Secondary Prevention of Coronary Heart Disease
Mode
   Aerobic exercise Walking, jogging, cycling, ergometry, elliptical trainers, stair climbing, rowing, cross-
country ski, aerobic dance
   Resistance training Hand weights, elastic bands, calisthenics, weight machines
Duration
   Aerobic exercise At least 20–30 min (preferably 30–45 min)
   Resistance exercise 10–15 repetitions; 1–3 sets of 8–10 different exercises for both upper and lower body
Frequency
   Aerobic exercise Most days (at least 4–5 d/wk and preferably 6–7 d/wk)
   Resistance exercise 2–3 sessions weekly (non-consecutive days)
Intensity
   Aerobic exercise Close to anaerobic threshold: 50–75% of peak V̇O2, 65–85% of maximal heart rate or
60–70% of heart rate reserve; 10–15 beats/min below the level of ischemia. Perceived
exertion scales can be used
   Resistance exercise Moderate intensity (should not be straining on last repetitions)

In fact, recent data on CRET have been particularly note-
worthy in elderly patients. Suaya et al153 demonstrated that
among elderly Medicare beneficiaries who attended CRET,
5-year mortality was reduced by 34%. Moreover, a very strong
relationship between greater CRET attainment (eg, number of
sessions) and mortality reduction was demonstrated. Hamill et
al also demonstrated the benefits of CRET in elderly Medicare
CHD patients, also noting a powerful relationship between
CRET attendance and lower mortality.154
Exercise Prescription in CHD
As mentioned earlier, there are guidelines for PA and ET in
primary prevention.2,3 In general, these recommendations also
apply to secondary prevention.97–99 In CRET programs and in
many clinicians’ offices, the prescription of aerobic and resis-
tance ET is needed and this frequently includes directions on
the mode of PA and ET, frequency, duration and intensity of
ET, which are all summarized in Table 2. Although most of
the emphasis in ET and secondary prevention is directed at
aerobic ET, we have recently demonstrated the importance of
muscular strength to predict survival in men with HTN,155 as
well as other populations,156 further supporting the perfor-
mance of resistance ET as the major means of improve mus-
cular strength.
In CRET programs, the ET prescription is the major
focus.97–99 However, whether patients with CHD are enrolled
in formal CRET or not, CHD patients should still be advised
to perform ET for at least 30 min (≥35 min to provide greater
caloric expenditure for the large number of overweight/obese
patients with CHD) on most days (at least 4–5 days/week, but
preferably 6–7 days/week). During CRET, intensity recom-
mendations are provided, based on exercise stress results and
depend on whether the exercise test was performed with ven-
tilatory expired gas exchange, as well as on the presence and
severity of exercise-induced ischemia. A major area of contro-
versy currently involves the relative risks vs. benefits of high-
intensity ET as opposed to low-moderate-intensity continu-
ous ET, and details on this topic are beyond the scope of this
review. In patients who are also shown to repeatedly demon-
strate that their exercise heart rate corresponds to a pre-
dicted level of perceived exertion, the Borg Scale of perceived
exertion or another simple scale can be used to monitor exer-
cise intensity.
In the office setting, outside of CRET programs, many clini-
cians have the opportunity to provide exercise prescription for
patients with CHD, as well as those at high risk of CHD, and
on many occasions, recent formal exercise stress testing results
may not be available. In these circumstances, ET intensity is
generally recommended at a “moderate” level (eg, the patient
should be able to speak during ET, but the exercise intensity
should be high enough such that one would prefer not to speak
for the majority of the ET session). As in many other instances
of medical care, if a simple 10-point perceived exertion scale
is used to describe exercise intensity, with 10 representing the
highest ET intensity possible and 0 describing rest, most ET
should be performed in the moderate range (approximately
5–7/10 intensity range).
Conclusions
Regular PA and ET and maintenance of high levels of CRF
have an important role in reducing CHD in both primary and
secondary prevention. In patients with CHD, CRET services
are markedly underutilized.157,158 Evidence suggests that ET
programs produce marked benefits in CRF, obesity indices,
lipids, inflammation, psychological risk factors, and other areas,
thus leading to reduction in major CV morbidity and mortality
in primary and secondary prevention. Through automatic refer-
ral and incentive-based systems geared to improve the quality
and delivery of medical care, greater emphasis must be placed
on the referral of all appropriate patients to CRET secondary
prevention programs after major CHD events.97–99,157,158
Disclosures
Financial Disclosure: None.
References
   1. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden
WB, et al. Heart disease and stroke statistics: 2012 update: A report
from the American Heart Association. Circulation 2012; 125:
e2 – e220.
   2. Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ,
Lee IM, et al. Quantity and quality of exercise for developing and
maintaining cardiorespiratory, musculoskeletal, and neuromotor
fitness in apparently healthy adults: Guidance for prescribing exer-
cise. Med Sci Sports Exerc 2011; 43: 1334 – 1359.
   3. U.S. Department of Health and Human Services. 2008 physical
activity guidelines for Americans. The Department, 2008.
   4. Hu G, Barengo NC, Tuomilehto J, Lakka TA, Nissinen A, Jousilahti
P. Relationship of physical activity and body mass index to the risk
of hypertension: A prospective study in Finland. Hypertension
 Advance Publication by-J-STAGE
Exercise and Coronary Prevention
2004; 43: 25 – 30.
   5. Paffenbarger RS, Wing AL, Hyde RT, Jung DL. Physical activity
and incidence of hypertension in college alumni. Am J Epidemiol  
1983; 117: 245 – 257.
   6. Pereira MA, Folsom AR, McGovern PG, Carpenter M, Arnett DK,
Liao D, et al. Physical activity and incident hypertension in black
and white adults: The Atherosclerosis Risk in Communities study.  
Prev Med 1999; 28: 304 – 312.
   7. Jebb SA, Moore MS. Contribution of a sedentary lifestyle and in-
activity to the etiology of overweight and obesity: Current evidence
and research issues. Med Sci Sports Exerc 1999; 31: S534 – S541.  
   8. Lahti-Koski M, Pietinen P, Heliövaara M, Vartiainen E. Associa-
tions of body mass index and obesity with physical activity, food
choices, alcohol intake, and smoking in the 1982–1997 FINRISK  
studies. Am J Clin Nutr 2002; 75: 809 – 817.
   9. Burchfiel CM, Sharp DS, Curb JD, Rodriguez BL, Hwang LJ,
Marcus EB, et al. Physical activity and incidence of diabetes: The  
Honolulu Heart Program. Am J Epidemiol 1995; 141: 360 – 368.
  10. Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS Jr. Physi-
cal activity and reduced occurrence of non-insulin-dependent dia-  
betes mellitus. N Engl J Med 1991; 325: 147 – 152.
  11. Kriska AM, Saremi A, Hanson RL, Bennett PH, Kobes S, Williams
DE, et al. Physical activity, obesity, and the incidence of type 2 dia-
betes in a high-risk population. Am J Epidemiol 2003; 158: 669 –    35. Rankinen T, Church TS, Rice T, Bouchard C, Blair SN. Cardiore-
675.
  12. Dunstan DW, Salmon J, Owen N, Armstrong T, Zimmet PZ, Welborn
TA, et al. Associations of TV viewing and physical activity with the  
metabolic syndrome in Australian adults. Diabetologia 2005; 48:
2254 – 2261.
  13. Irwin ML, Ainsworth BE, Mayer-Davis EJ, Addy CL, Pate RR,  
Durstine JL. Physical activity and the metabolic syndrome in a tri-
ethnic sample of women. Obes Res 2002; 10: 1030 – 1037.
  14. Rennie K, McCarthy N, Yazdgerdi S, Marmot M, Brunner E. As-
sociation of the metabolic syndrome with both vigorous and moder-  
ate physical activity. Int J Epidemiol 2003; 32: 600 – 606.
  15. Barengo NC, Hu G, Lakka TA, Pekkarinen H, Nissinen A,
Tuomilehto J. Low physical activity as a predictor for total and
cardiovascular disease mortality in middle-aged men and women in  
Finland. Eur Heart J 2004; 25: 2204 – 2211.
  16. Hu FB, Willett WC, Li T, Stampfer MJ, Colditz GA, Manson JE.
Adiposity as compared with physical activity in predicting mortal-
ity among women. N Engl J Med 2004; 351: 2694 – 2703.  
  17. Hu G, Eriksson J, Barengo NC, Lakka TA, Valle TT, Nissinen A,
et al. Occupational, commuting, and leisure-time physical activity in
relation to total and cardiovascular mortality among Finnish subjects
with type 2 diabetes. Circulation 2004; 110: 666 – 673.  
  18. Hu G, Jousilahti P, Borodulin K, Barengo NC, Lakka TA, Nissinen
A, et al. Occupational, commuting and leisure-time physical activ-
ity in relation to coronary heart disease among middle-aged Finnish
men and women. Atherosclerosis 2007; 194: 490 – 497.
  19. Paffenbarger RS, Hyde RT, Wing AL, Hsieh CC. Physical activity,  
all-cause mortality, and longevity of college alumni. N Engl J Med
1986; 314: 605 – 613.
  20. Slattery ML, Jacobs DR Jr, Nichaman MZ. Leisure time physical  
activity and coronary heart disease death: The US Railroad Study.
Circulation 1989; 79: 304 – 311.
  21. Smith GD, Shipley MJ, Batty GD, Morris JN, Marmot M. Physical
activity and cause-specific mortality in the Whitehall study. Public  
Health 2000; 114: 308 – 315.
  22. Sesso HD, Paffenbarger RS, Lee IM. Physical activity and coronary
heart disease in men. Circulation 2000; 102: 975 – 980.
  23. Lee IM, Rexrode KM, Cook NR, Manson JE, Buring JE. Physical  
activity and coronary heart disease in women: Is “no pain, no gain”
passé? JAMA 2001; 285: 1447 – 1454.
  24. Li TY, Rana JS, Manson JE, Willett WC, Stampfer MJ, Colditz
GA, et al. Obesity as compared with physical activity in predicting
risk of coronary heart disease in women. Circulation 2006; 113:  
499 – 506.
  25. Li J, Siegrist J. Physical activity and risk of cardiovascular disease:
A meta-analysis of prospective cohort studies. Int J Environ Res
Public Health 2012; 9: 391 – 407.  
  26. Sofi F, Capalbo A, Cesari F, Abbate R, Gensini GF. Physical activity
during leisure time and primary prevention of coronary heart disease:
An updated meta-analysis of cohort studies. Eur J Cardiovasc Prev
Rehabil 2008; 15: 247 – 257.  
  27. Bijnen FC, Caspersen CJ, Feskens EJ, Saris WH, Mosterd WL,
Kromhout D. Physical activity and 10-year mortality from cardio-
vascular diseases and all causes: The Zutphen Elderly Study. Arch
Intern Med 1998; 158: 1499 – 1505.  
  28. Fang J, Wylie-Rosett J, Cohen HW, Kaplan RC, Alderman MH.
Exercise, body mass index, caloric intake, and cardiovascular mor-
tality. Am J Prev Med 2003; 25: 283 – 289.
29. Weinstein AR, Sesso HD, Lee IM, Rexrode KM, Cook NR, Manson
JE, et al. The joint effects of physical activity and body mass index
on coronary heart disease risk in women. Arch Intern Med 2008;
168: 884 – 890.
30. Paffenbarger RS, Hyde RT, Wing AL, Lee IM, Jung DL, Kampert
JB. The association of changes in physical-activity level and other
lifestyle characteristics with mortality among men. N Engl J Med
1993; 328: 538 – 545.
31. Gregg EW, Cauley JA, Stone K, Thompson TJ, Bauer DC, Cummings
SR, et al. Relationship of changes in physical activity and mortality
among older women. JAMA 2003; 289: 2379 – 2386.
32. Wannamethee SG, Shaper AG, Walker M. Changes in physical
activity, mortality, and incidence of coronary heart disease in older
men. Lancet 1998; 351: 1603 – 1608.
33. American College of Sports Medicine. ACSM’s guidelines for ex-
ercise testing and prescription. Baltimore: Lippincott Williams&
Williams, 2010.
34. Barlow CE, LaMonte MJ, FitzGerald SJ, Kampert JB, Perrin JL,
Blair SN. Cardiorespiratory fitness is an independent predictor of
hypertension incidence among initially normotensive healthy women.
Am J Epidemiol 2006; 163: 142 – 150.
spiratory fitness, BMI, and risk of hypertension: The HYPGENE
study. Med Sci Sports Exerc 2007; 39: 1687 – 1692.
36. Ross R, Katzmarzyk PT. Cardiorespiratory fitness is associated
with diminished total and abdominal obesity independent of body
mass index. Int J Obes Relat Metab Disord 2003; 27: 20437.
37. Wong SL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN,
Ross R. Cardiorespiratory fitness is associated with lower abdomi-
nal fat independent of body mass index. Med Sci Sports Exerc 2004;
36: 286 – 291.
38. Laaksonen DE, Lakka HM, Salonen JT, Niskanen LK, Rauramaa
R, Lakka TA. Low levels of leisure-time physical activity and
cardiorespiratory fitness predict development of the metabolic syn-
drome. Diabetes Care 2002; 25: 1612 – 1618.
39. LaMonte MJ, Barlow CE, Jurca R, Kampert JB, Church TS, Blair
SN. Cardiorespiratory fitness is inversely associated with the inci-
dence of metabolic syndrome: A prospective study of men and
women. Circulation 2005; 112: 505 – 512.
40. Shuval K, Finley CE, Chartier KG, Balasubramanian BA, Gabriel
KP, Barlow CE. Cardiorespiratory fitness, alcohol intake, and met-
abolic syndrome incidence in men. Med Sci Sports Exerc 2012; 44:
2125 – 2131.
41. Lynch J, Helmrich SP, Lakka TA, Kaplan GA, Cohen RD, Salonen
R, et al. Moderately intense physical activities and high levels of
cardiorespiratory fitness reduce the risk of non-insulin-dependent
diabetes mellitus in middle-aged men. Arch Intern Med 1996; 156:
1307 – 1314.
42. Sawada SS, Lee IM, Muto T, Matuszaki K, Blair SN. Cardiorespi-
ratory fitness and the incidence of type 2 diabetes. Diabetes Care
2003; 26: 2918 – 2922.
43. Sieverdes JC, Sui X, Lee DC, Church TS, McClain A, Hand GA,
et al. Physical activity, cardiorespiratory fitness and the incidence
of type 2 diabetes in a prospective study of men. Br J Sports Med
2010; 44: 238 – 244.
44. Blair SN, Kampert JB, Kohl HW 3rd, Barlow CE, Macera CA,
Paffenbarger RS Jr, et al. Influences of cardiorespiratory fitness and
other precursors on cardiovascular disease and all-cause mortality
in men and women. JAMA 1996; 276: 205 – 210.
45. Mora S, Redberg RF, Cui Y, Whiteman MK, Flaws JA, Sharrett
AR, et al. Ability of exercise testing to predict cardiovascular and
all-cause death in asymptomatic women: A 20-year follow-up of
the Lipid Research Clinics Prevalence study. JAMA 2003; 290:
1600 – 1607.
46. Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, Asumi M, et al.
Cardiorespiratory fitness as a quantitative predictor of all-cause mor-
tality and cardiovascular events in healthy men and women. JAMA
2009; 301: 2024 – 2035.
47. Katzmarzyk PT, Church TS, Blair SN. Cardiorespiratory fitness
attenuates the effects of the metabolic syndrome on all-cause and
cardiovascular disease mortality in men. Arch Intern Med 2004;
164: 1092 – 1097.
48. Lyerly GW, Sui X, Lavie CJ, Church TS, Hand GA, Blair SN. The
association between cardiorespiratory fitness and risk of all-cause
mortality among women with impaired fasting glucose or undiag-
nosed diabetes mellitus. Mayo Clin Proc 2009; 84: 780 – 786.
49. McAuley P, Myers J, Emerson B, Oliveira RB, Blue CL, Pittsley J,
et al. Cardiorespiratory fitness and mortality in diabetic men with
 Advance Publication by-J-STAGE
and without cardiovascular disease. Diabetes Res Clin Pract 2009;
85: e30 – e33.
  50. Berry JD, Willis B, Gupta S, Barlow CE, Lakoski SG, Khera A, et  
al. Lifetime risks for cardiovascular disease mortality by cardiorespi-
ratory fitness levels measured at ages 45, 55, and 65 years in Menthe
Cooper Center Longitudinal Study. J Am Coll Cardiol 2011; 57:
1604 – 1610.  
  51. Church TS, LaMonte MJ, Barlow CE, Blair SN. Cardiorespiratory
fitness and body mass index as predictors of cardiovascular disease
mortality among men with diabetes. Arch Intern Med 2005; 165:  
2114 – 2120.
  52. Farrell SW, Kampert JB, Kohl HW 3rd, Barlow CE, Macera CA,
Paffenbarger RS Jr, et al. Influences of cardiorespiratory fitness
levels and other predictors on cardiovascular disease mortality in  
men. Med Sci Sports Exerc 1998; 30: 899 – 905.
  53. Stevens J, Cai J, Evenson KR, Thomas R. Fitness and fatness as
predictors of mortality from all causes and from cardiovascular dis-  
ease in men and women in the Lipid Research Clinics Study. Am J
Epidemiol 2002; 156: 832 – 841.
  54. Stevens J, Evenson KR, Thomas O, Cai J, Thomas R. Associations
of fitness and fatness with mortality in Russian and American men  
in the Lipids Research Clinics Study. Int J Obes Relat Metab Dis-
ord 2004; 28: 1463 – 1470.
  55. Wei M, Kampert JB, Barlow CE, Nichaman MZ, Gibbons LW,  
Paffenbarger RS Jr, et al. Relationship between low cardiorespira-
tory fitness and mortality in normal-weight, overweight, and obese
men. JAMA 1999; 282: 1547 – 1553.  
  56. Lee CD, Blair SN, Jackson AS. Cardiorespiratory fitness, body com-
position, and all-cause and cardiovascular disease mortality in men.
Am J Clin Nutr 1999; 69: 373 – 380.
  57. Blair SN, Kohl HW III, Barlow CE, Paffenbarger RS Jr, Gibbons  
LW, Macera CA. Changes in physical fitness and all-cause mortal-
ity: A prospective study of healthy and unhealthy men. JAMA 1995;
273: 1093 – 1098.
  58. Erikssen G, Liestol K, Bjornholt J, Thaulow E, Sandvik L, Erikssen  
J. Changes in physical fitness and changes in mortality. Lancet 1998;
352: 759 – 762.
  59. Lee DC, Sui X, Artero EG, Lee IM, Church TS, McAuley PA, et al.
Long-term effects of changes in cardiorespiratory fitness and body  
mass index on all-cause and cardiovascular disease mortality in
men: The Aerobics Center Longitudinal Study. Circulation 2011;
124: 2483 – 2490.
  60. Lee DC, Sui X, Ortega FB, Kim YS, Church TS, Winett RA, et al.  
Comparisons of leisure-time physical activity and cardiorespiratory
fitness as predictors of all-cause mortality in men and women. Br J
Sports Med 2011; 45: 504 – 510.
  61. Williams PT. Physical fitness and activity as separate heart disease  
risk factors: A meta-analysis. Med Sci Sports Exerc 2001; 33: 754 –  Kenny GP. Associations between physical fitness and HbA1c in type
761.
  62. Sassen B, Cornelissen VA, Kiers H, Wittink H, Kok G, Vanhees L.  
Physical fitness matters more than physical activity in controlling
cardiovascular disease risk factors. Eur J Cardiovasc Prev Rehabil
2009; 16: 677 – 683.  
  63. Blair SN, Cheng Y, Scott Holder J. Is physical activity or physical
fitness more important in defining health benefits? Med Sci Sports
Exerc 2001; 33: S379 – S399.
  64. Fagard R, Bielen E, Amery A. Heritability of aerobic power and  
anaerobic energy generation during exercise. J Appl Phsiol 1991; 70:
357 – 362.
  65. Colberg SR, Albright AL, Bissmer BJ, Braun B, Chasan-Taber L,
Fernhall B, et al. Exercise and type 2 diabetes: American College of
Sports Medicine and the American Diabetes Association: Joint posi-  
tion statement: Exercise and type 2 diabetes. Med Sci Sports Exerc
2010; 42: 2282 – 2303.
  66. Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA,
et al. Physical activity and public health: Updated recommendation
for adults from the American College of Sports Medicine and the  
American Heart Association. Med Sci Sports Exerc 2007; 39: 1423 –  Stacpoole PW. Exercise training, without weight loss, increases in-
1434.
  67. National Institute of Health. Physical activity and cardiovascular
health: NIH Consensus Development Panel on Physical Activity  
and Cardiovascular Health. JAMA 1996; 276: 241 – 246.
  68. Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB,
McCartney JS, et al. Effects of the amount and intensity of exercise
on plasma lipoproteins. N Engl J Med 2002; 347: 1483 – 1492.  
  69. Church TS, Earnest CP, Skinner JS, Blair SN. Effects of different
doses of physical activity on cardiorespiratory fitness among sed-
entary, overweight or obese postmenopausal women with elevated
blood pressure. JAMA 2007; 297: 2081 – 2091.  
  70. Crouse SF, O’Brien BC, Grandjean PW, Lowe RC, Rohack JJ,
SWIFT DL et al.
Green JS, et al. Training intensity, blood lipids, and apolipoproteins
in men with high cholesterol. J Appl Physiol 1997; 82: 270 – 277.
71. O’Donovan G, Owen A, Bird SR, Kearney EM, Nevill AM, Jones
DW, et al. Changes in cardiorespiratory fitness and coronary heart
disease risk factors following 24 wk of moderate- or high-intensity
exercise of equal energy cost. J Appl Physiol 2005; 98: 1619 – 1625.
72. Boulé NG, Kenny GP, Haddad E, Wells GA, Sigal RJ. Meta-analy-
sis of the effect of structured exercise training on cardiorespiratory
fitness in type 2 diabetes mellitus. Diabetologia 2003; 46: 1071 – 108.
73. DiPietro L, Dziura J, Yeckel CW, Neufer PD. Exercise and im-
proved insulin sensitivity in older women: Evidence of the enduring
benefits of higher intensity training. J Appl Physiol 2006; 100: 142 – 
149.
74. Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS,
Kraus WE. Effect of the volume and intensity of exercise training
on insulin sensitivity. J Appl Physiol 2004; 96: 101 – 106.
75. Irving BA, Davis CK, Brock DW, Weltman JY, Swift D, Barrett EJ,
et al. Effect of exercise training intensity on abdominal visceral fat
and body composition. Med Sci Sports Exerc 2008; 40: 1863 – 
1872.
76. Swain DP, Franklin BA. Comparison of cardioprotective benefits
of vigorous versus moderate intensity aerobic exercise. Am J Car-
diol 2006; 97: 141 – 147.
77. Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB,
McCartney JS, et al. Effects of the amount and intensity of exercise
on plasma lipoproteins. N Engl J Med 2002; 347: 1483 – 1492.
78. Tambalis K, Panagiotakos DB, Kavouras SA, Sidossis LS. Re-
sponses of blood lipids to aerobic, resistance, and combined aerobic
with resistance exercise training: A systematic review of current
evidence. Angiology 2009; 60: 614 – 632.
79. Kodama S, Tanaka S, Saito K, Shu M, Sone Y, Onitake F, et al.
Effect of aerobic exercise training on serum levels of high-density
lipoprotein cholesterol: A meta-analysis. Arch Intern Med 2007;
167: 999 – 1008.
80. Church TS, Blair SN, Cocreham S, Johannsen N, Johnson W,
Kramer K, et al. Effects of aerobic and resistance training on hemo-
globin A1c levels in patients with type 2 diabetes: A randomized
controlled trial. JAMA 2010; 304: 2253 – 2262.
81. Sigal RJ, Kenny GP, Boule NG, Wells GA, Prud’homme D, Fortier
M, et al. Effects of aerobic training, resistance training, or both on
glycemic control in type 2 diabetes: A randomized trial. Ann Intern
Med 2007; 147: 357 – 369.
82. Bacchi E, Negri C, Zanolin ME, Milanese C, Faccioli N, Trombetta
M, et al. Metabolic effects of aerobic training and resistance train-
ing in type 2 diabetic subjects: A randomized controlled trial (the
RAED2 study). Diabetes Care 2012; 35: 676 – 682.
83. Larose J, Sigal RJ, Khandwala F, Prud’homme D, Boulé NG,
2 diabetes mellitus. Diabetologia 2011; 54: 93 – 102.
84. Larose J, Sigal RJ, Boulé NG, Wells GA, Prud’homme D, Fortier
MS, et al. Effect of exercise training on physical fitness in type II
diabetes mellitus. Med Sci Sports Exerc 2010; 42: 1439 – 1447.
85. Katzmarzyk PT, Leon AS, Wilmore JH, Skinner JS, Rao DC,
Rankinen T, et al. Targeting the metabolic syndrome with exercise:
Evidence from the Heritage Family Study. Med Sci Sports Exerc
2003; 35: 1703 – 1709.
86. Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith
BK, et al. American College of Sports and Medicine Position Stand:
Appropriate physical activity intervention strategies for weight loss
and prevention of weight regain for adults. Med Sci Sports Exerc
2009; 41: 459 – 471.
87. Donnelly JE, Hill JO, Jacobsen DJ, Potteiger J, Sullivan DK, Johnson
SL, et al. Effects of a 16-month randomized controlled exercise trial
on body weight and composition in young, overweight men and
women: The Midwest Exercise Trial. Arch Intern Med 2003; 163:
1343 – 1350.
88. Duncan GE, Perri MG, Theriaque DW, Hutson AD, Eckel RH,
sulin sensitivity and postheparin plasma lipase activity in previously
sedentary adults. Diabetes Care 2003; 26: 557 – 562.
89. Dekker MJ, Lee S, Hudson R, Kilpatrick K, Graham TE, Ross R,
et al. An exercise intervention without weight loss decreases circu-
lating interleukin-6 in lean and obese men with and without type 2
diabetes mellitus. Metabolism 2007; 56: 332 – 338.
90. Lee S, Kuk JL, Davidson LE, Hudson R, Kilpatrick K, Graham TE,
et al. Exercise without weight loss is an effective strategy for obe-
sity reduction in obese individuals with and without type 2 diabetes.
J Appl Physiol 2005; 99: 1220 – 1225.
91. Thompson PD, Yurgalevitch SM, Flynn MM, Zmuda JM, Spannaus-
Martin D, Saritelli A, et al. Effect of prolonged exercise training
 Advance Publication by-J-STAGE
Exercise and Coronary Prevention
without weight loss on high-density lipoprotein metabolism in over-
weight men. Metabolism 1997; 46: 217 – 223.
  92. Johnson NA, Sachinwalla T, Walton DW, Smith K, Armstrong A,
Thompson MW, et al. Aerobic exercise training reduces hepatic and
visceral lipids in obese individuals without weight loss. Hepatology
2009; 50: 1105 – 1112.
  93. Pescatello LS, Franklin BA, Fagard R, Farquhar WB, Kelley GA,
Ray CA; American College of Sports Medicine. American College
of Sports Medicine position stand: Exercise and hypertension. Med
Sci Sports Exerc 2004; 36: 533 – 553.
  94. Whelton SP, Chin A, Xue X, Jiang H. Effect of aerobic exercise on
blood pressure: A meta-analysis of randomized, controlled trials.
Ann Intern Med 2002; 136: 493.
  95. Cornelissen VA, Fagard RH. Effects of endurance training on blood
pressure, blood pressure-regulating mechanisms, and cardiovascu-
lar risk factors. Hypertension 2005; 46: 667 – 675.
  96. Edward Stanley, Earl of Derby. The conduct of life. Address at
Liverpool College, December 20, 1873.
  97. Lavie CJ, Thomas RJ, Squires RW, Allison TG, Milani RV. Exer-
cise training and cardiac rehabilitation in primary and secondary
prevention of coronary heart disease. Mayo Clin Proc 2009; 84:
373 – 383.
  98. Lavie CJ, Milani RV. Cardiac rehabilitation and exercise training
in secondary coronary heart disease prevention. Prog Cardiovasc
Dis 2011; 53: 397 – 403.
  99. Lavie CJ, Milani RV, Arena RA. Exercise-based cardiac rehabilita-
tion: Outcomes and expectations. CRC Press. In: Rippe J, editor.
Lifestyle medicine. Boca Raton, FL, 2013 (in press).
100. Milani RV, Lavie CJ, Spiva H. Limitations of estimating metabolic
equivalents in exercise assessment in patients with coronary artery
disease. Am J Cardiol 1995; 75: 940 – 942.
101. Lavie CJ, Milani RV. Disparate effects of improving aerobic exer-
cise capacity and quality of life after cardiac rehabilitation in young
and elderly coronary patients. J Cardiopulm Rehabil 2000; 20: 235 –  Coll Cardiol 2011; 53: 2651 – 2653.
240.
102. Lavie CJ, Milani RV. Metabolic equivalent (MET) inflation – not
the MET we used to know [editorial]. J Cardiopulm Rehabil Prev
2007; 27: 149 – 150.
103. Lavie CJ, Swift DL, Johannsen NM, Arena R, Church TS. Physical
fitness: An often forgotten cardiovascular risk factor. J Glycom
Lipidom 2012; 2: e104.
104. Lavie CJ, Milani RV. Patients with high baseline exercise capacity
benefit from cardiac rehabilitation and exercise training programs.
Am Heart J 1994; 128: 1105 – 1109.
105. Kavanagh T, Mertens DJ, Hamm LF, Beyene J, Kennedy J, Corey
P, et al. Prediction of long-term prognosis in 12 169 men referred
for cardiac rehabilitation. Circulation 2002; 106: 666 – 671.
106. Kavanagh T, Mertens DJ, Hamm LF, Beyene J, Kennedy J, Corey
P, et al. Peak oxygen intake and cardiac mortality in women re-
ferred for cardiac rehabilitation. J Am Coll Cardiol 2003; 42: 2139 –  paradox in heart failure. J Card Fail 2011; 17: 381 – 383.
2143.
107. Vanhees L, Fagard R, Thijs L, Amery A. Prognostic value of train-
ing-induced change in peak exercise capacity in patients with myo-
cardial infarcts and patients with coronary bypass surgery. Am J
Cardiol 1995; 76: 1014 – 1019.
108. Lavie CJ, Milani RV, O’Keefe JH. Does the choice of statin really
matter? Postgrad Med 2010; 122: 243 – 247.
109. Lavie CJ, Milani RV. High-dose atorvastatin in acute coronary and
cerebrovascular syndromes. J Am Coll Cardiol Intv 2010; 3: 340 –  disease: Impact of lean mass index and body fat in the “obesity
342.
110. Lavie CJ, Milani RV, O’Keefe JH. Statin wars: Emphasis on po-
tency vs event reduction and safety? Mayo Clin Proc 2007; 82:
539 – 542.
111. Milani RV. Lavie CJ. Prevalence and effects of nonpharmacologic
treatment of “isolated” low-HDL cholesterol in patients with coro-
nary artery disease. J Cardiolpulm Rehab 1995; 15: 439 – 444.
112. Lavie CJ, Milani RV. Effects of nonpharmacologic therapy with
cardiac rehabilitation and exercise training in patients with low levels
of high-density lipoprotein cholesterol. Am J Cardiol 1996; 78: 1286 –  reduction in patients with cardiovascular disease. Curr Treat Op-
1289.
113. Lavie CJ, Milani RV. Effects of cardiac rehabilitation and exercise
training on low density lipoprotein cholesterol in patients with hy-
pertriglyceridemia and coronary artery disease. Am J Cardiol 1994;
74: 1192 – 1195.
114. Lavie CJ, Milani RV, Verma A, O’Keefe JH. C-reactive protein and
cardiovascular diseases: Is it ready for primitive? Am J Med Sci
2009; 338: 486 – 492.
115. Musunuru K, Kral BG, Blumenthal RS. The use of high-sensitivity
assays for C-reactive protein in clinical practice. Nat Clin Pract
Cardiovasc Med 2008; 5: 621 – 635.
116. Lavie CJ, Church TS, Milani RV, Earnest CP. Impact of physical
activity, cardiorespiratory fitness, and exercise training on markers
of inflammation. J Cardiopulm Rehabil Prev 2011; 31: 137 – 145.
117. Milani RV, Lavie CJ, Mehra MR. Reduction in C-reactive protein
through cardiac rehabilitation and exercise training. J Am Coll Car-
diol 2004; 43: 1056 – 1061.
118. Milani RV, Lavie CJ. Prevalence and profile of metabolic syndrome
in patients following acute coronary events and effects of therapeu-
tic lifestyle change with cardiac rehabilitation. Am J Cardiol 2003;
92: 50 – 54.
119. Lavie CJ, Morshedi-Meibodi A, Milani RV. Impact of cardiac reha-
bilitation on coronary risk factors, inflammation, and the metabolic
syndrome in obese coronary patients. J Cardiometab Syndr 2008; 3:
136 – 140.
120. Lavie CJ, Milani RV, Artham SM, Patel DA, Ventura HO. The obe-
sity paradox, weight loss, and coronary disease. Am J Med 2009;
122: 1106 – 1114.
121. Ades PA, Savage PD, Toth MJ, Harvey-Berino J, Schneider DJ,
Bunn JY, et al. High-calorie-expenditure exercise: A new approach
to cardiac rehabilitation for overweight coronary patients. Circula-
tion 2009; 119: 2671 – 2678.
122. Caulin-Glaser T, Falko J, Hindman L, LaLonde M, Snow R. Car-
diac rehabilitation is associated with an improvement in C-reactive
protein levels in both men and women with cardiovascular disease.
J Cardiopulm Rehabil 2005; 25: 332 – 336 [quiz 337 – 338].
123. McAuley PA, Artero EG, Sui X, Lee DC, Church TS, Lavie CJ, et
al. The obesity paradox, cardiorespiratory fitness, and coronary heart
disease. Mayo Clin Proc 2012; 87: 443 – 451.
124. Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular
disease: Risk factor, paradox, and impact of weight loss. J Am Coll
Cardiol 2009; 53: 1925 – 1932.
125. Lavie CJ, Milani RV, Ventura HO. Impact of obesity on outcomes
in myocardial infarction: Combating the “obesity paradox”. J Am
126. Lavie CJ, Milani RV, Ventura HO, Romero-Corral A. Body com-
position and heart failure prevalence and prognosis: Getting to the
fat of the matter in the “obesity paradox”. Mayo Clin Proc 2010;
85: 605 – 608.
127. Lavie CJ, Milani RV, Ventura HO, Cardenas GA, Mehra MR, Messerli
FH. Disparate effects of left ventricular geometry and obesity on
mortality in patients with preserved left ventricular ejection fraction.
Am J Cardiol 2007; 100: 1460 – 1464.
128. Lavie CJ, De Schutter A, Patel D, Artham SM, Milani RV. Body
composition and coronary heart disease mortality: An obesity or a
lean paradox? Mayo Clin Proc 2011; 86: 857 – 864.
129. Lavie CJ, Osman AF, Milani RV, Mehra MR. Body composition
and prognosis in chronic systolic heart failure: The obesity paradox.
Am J Cardiol 2003; 91: 891 – 894.
130. Lavie CJ, Ventura HO. Weighing in on obesity and the obesity
131. Lavie CJ, Milani RV. Weight reduction and improvements in en-
dothelial function: Combating the “obesity paradox” in coronary
heart disease. Chest 2011; 140: 1395 – 1396.
132. Arena R, Lavie CJ. Excess body weight and coronary artery dis-
ease: Associated risks, the obesity paradox, and implications for car-
diac rehabilitation. US Cardiol 2011; 8: 88 – 93.
133. Lavie CJ, De Schutter A, Patel DA, Romero-Corral A, Artham SM,
Milani RV. Body composition and survival in stable coronary heart
paradox”. J Am Coll Cardiol 2012; 60: 1374 – 1380.
134. Lavie CJ, Alpert MA, Arena R, Mehra MR, Milani RV, Ventura
HO. Impact of obesity on prevalence and the obesity paradox on
prognosis in heart failure. J Am Coll Cardiol Heart Fail 2013 (in
press).
135. Lavie CJ, Cahalin LP, Chase P, Myers J, Bensimhon D, Peberdy
MA, et al. Impact of cardiorespiratory fitness on the obesity para-
dox in patients with heart failure. Mayo Clin Proc 2013 (in press).
136. Artham SM, Lavie CJ, Milani RV, Ventura HO. Value of weight
tions Cardiovasc Med 2010; 12: 21 – 35.
137. Lavie CJ, Milani RV. Effects of cardiac rehabilitation, exercise
training, and weight reduction on exercise capacity, coronary risk
factors, behavioral characteristics, and quality of life in obese coro-
nary patients. Am J Cardiol 1997; 79: 397 – 401.
138. Sierra-Johnson J, Romero-Corral A, Somers VK, Lopez-Jimenez F,
Thomas RJ, Squires RW, et al. Prognostic importance of weight
loss in patients with coronary heart disease regardless of initial body
mass index. Eur J Cardiovasc Prev Rehabil 2008; 15: 336 – 340.
139. Eilat-Adar S, Eldar M, Goldbourt U. Association of intentional
changes in body weight with coronary heart disease event rates in
 Advance Publication by-J-STAGE
overweight subjects who have an additional coronary risk factor.
Am J Epidemiol 2005; 161: 352 – 358.
140. Cicero. On old age. Vol 9, Part 2. The Harvard Classics. Shuck-
burgh ES, translator/editor. New York, NY: PF Collier and Son,
1909 –14; 10.
141. Lavie CJ, Milani RV, O’Keefe JH, Lavie TJ. Impact of exercise
training on psychological risk factors. Prog Cardiovasc Dis 2011;
53: 464 – 470.
142. Lavie CJ, Milani RV. Prevalence of anxiety in coronary patients with
improvement following cardiac rehabilitation and exercise training.
Am J Cardiol 2004; 93: 336 – 339.
143. Lavie CJ, Milani RV. Adverse psychological and coronary risk pro-
files in young patients with coronary artery disease and benefits
of formal cardiac rehabilitation. Arch Intern Med 2006; 166: 1878 –  154. Hammill BG, Curtis LH, Schulman KA, Whellan DJ. Relationship
1883.
144. Lucini D, Milani RV, Costantino G, Lavie CJ, Porta A, Pagani M.
Effects of cardiac rehabilitation and exercise training on autonomic
regulation in patients with coronary artery disease. Am Heart J
2002; 143: 977 – 983.
145. Milani RV, Lavie CJ. Impact of cardiac rehabilitation on depression
and its associated mortality. Am J Med 2007; 120: 799 – 806.
146. Milani RV, Lavie CJ, Mehra MR, Ventura HO. Impact of exercise
training and depression on survival in heart failure due to coronary
heart disease. Am J Cardiol 2011; 107: 64 – 68.
147. Artham SM, Lavie CJ, Milani RV. Cardiac rehabilitation programs
markedly improve high-risk profiles in coronary patients with high
psychological distress. South Med J 2008; 101: 262 – 267.
148. Milani RV, Lavie CJ. Reducing psychosocial stress: A novel mech-
anism of improving survival from exercise training. Am J Med
2009; 122: 931 – 938.
149. O’Connor GT, Buring JE, Yusuf S, Goldhaber SZ, Olmstead EM,
Paffenbarger RS Jr, et al. An overview of randomized trials of re-
habilitation with exercise after myocardial infarction. Circulation
1989; 80: 234 – 244.
SWIFT DL et al.
150. Jolliffe JA, Rees K, Taylor RS, Thompson D, Oldridge N, Ebrahim
S. Exercise-based rehabilitation for coronary heart disease. Co-
chrane Database Syst Rev 2001; (1): CD001800.
151. Witt BJ, Jacobsen SJ, Weston SA, Killian JM, Meverden RA,
Allison TG, et al. Cardiac rehabilitation after myocardial infarction
in the community. J Am Coll Cardiol 2004; 44: 988 – 996.
152. Goel K, Lennon RJ, Tilbury T, Squires RW, Thomas RJ. Impact of
cardiac rehabilitation on mortality and cardiovascular events after
percutaneous coronary intervention in the community. Circulation
2011; 123: 2344 – 2352.
153. Suaya JA, Stason WB, Ades PA, Normand SL, Shepard DS. Car-
diac rehabilitation and survival in older coronary patients. J Am
Coll Cardiol 2009; 54: 25 – 33.
between cardiac rehabilitation and long-term risks of death and
myocardial infarction among elderly Medicare beneficiaries. Cir-
culation 2010; 121: 63 – 70.
155. Artero EG, Lee DC, Ruiz JR, Sui X, Ortega FB, Church TS, et al.
A prospective study of muscular strength and all-cause mortality in
men with hypertension. J Am Coll Cardiol 2011; 57: 1831 – 1837.
156. Artero EG, Lee DC, Lavie CJ, Espana-Romero V, Sui X, Church
TS, et al. Effects of muscular strength on cardiovascular risk factors
and prognosis. J Cardiopulm Rehabil Prev 2012; 32: 351 – 358.
157. Arena R, Williams M, Forman DE, Cahalin LP, Coke L, Myers J,
et al. Increasing referral and participation rates to outpatient cardiac
rehabilitation: The valuable role of healthcare professionals in the
inpatient and home health settings: A science advisory from the
American Heart Association. Circulation 2012; 125: 1321 – 1329.
158. Balady GJ, Ades PA, Bittner VA, Franklin BA, Gordon NF, Thomas
RJ, et al. Referral, enrollment and delivery of cardiac rehabilitation/
secondary prevention programs at clinical centers and beyond: A
presidential advisory from the American Heart Association. Circula-
tion 2011; 124: 2951 – 2960.