- Email: [email protected]
Exercise for Coronary Heart Disease Patients
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 70, NO. 14, 2017
ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jacc.2017.08.016
EDITORIAL COMMENT
Exercise for Coronary Heart Disease Patients Little Is Good, More Is Better, Vigorous Is Best* Thijs M.H. Eijsvogels, PHD,a,b Martijn F.H. Maessen, PHDa
T
he
cardiovascular
health
benefits
of
a
and mortality in 15,486 patients with stable CHD who
physically active lifestyle are well recognized
participated
and frequently described (1,2). Nevertheless,
Atherosclerotic Plaque by Initiation of Darapladib
physical inactivity remains a global problem, particu-
Therapy) trial. Patients from 39 countries were allo-
larly in clinical populations such as coronary heart
cated to tertiles of PA. The intermediate and most
disease
active tertile had a lower risk for all-cause mortality
(CHD) patients. A recent meta-analysis
in
the
STABILITY
(Stabilization
of
including >1,000,000 individuals found that individ-
(hazard ratio [HR]: 0.75; 95% confidence interval [CI]:
uals who are inactive and sit the most have the
0.65 to 0.87, and HR: 0.70; 95% CI: 0.60 to 0.82),
highest risk for mortality (3). The typical CHD patient
cardiovascular mortality (HR: 0.89; 95% CI: 0.74 to
fits this description as she or he usually performs
1.06, and HR: 0.71; 95% CI: 0.58 to 0.88), and non-
little regular exercise and sits much of the time. Stra-
cardiovascular mortality (HR: 0.54; 95% CI: 0.41 to
tegies to increase physical activity (PA) and decrease
0.72, and HR: 0.73; 95% CI: 0.55 to 0.96) compared
sitting in high-risk populations such as CHD patients
with the least active tertile. The most active tertile
are therefore needed. Current guidelines prescribe
also had a lower risk for major adverse coronary
similar PA recommendations for primary (4) and sec-
events (HR: 0.81; 95% CI: 0.71 to 0.92), whereas
ondary prevention (5,6): 150 min/week of exercise at
there were no differences in the risk for myocardial
a moderate intensity. Most evidence for the health
infarction and stroke across all tertiles. The dose-
benefits of exercise in CHD patients are derived
response analysis showed a curvilinear relationship
from cardiac rehab studies (7). Although these find-
between PA and mortality with the largest risk re-
ings support the benefits of regular PA, these studies
ductions at the beginning of the curve. Furthermore,
do not inform on the minimal dose, optimal dose, and
the PA-associated reductions in mortality were greater
potential upper limit of PA to reduce cardiovascular
among CHD patients, whose exercise was limited by
morbidity and mortality.
dyspnea and in those with a high STABILITY CHD risk
SEE PAGE 1689
score, suggesting that high-risk patients benefit the most from a physically active lifestyle.
In this issue of the Journal, Stewart et al. (8)
This study provides important insight in the health
describe the association between self-reported PA
benefits of exercise training and habitual PA in CHD patients. Data from Stewart et al. (8) suggest that as little as 10 min/day of brisk walking (i.e., 3.5 mph) is
*Editorials published in the Journal of the American College of Cardiology
associated with a 33% risk reduction for all-cause
reflect the views of the authors and do not necessarily represent the
mortality. For those unable to walk at a brisk pace,
views of JACC or the American College of Cardiology.
15 to 20 min/day at a slower pace (2 to 2.5 mph) will
From the Radboud Institute for Health Sciences, Department of Physi-
yield similar benefits (8). These findings suggest that
ology, Radboud University Medical Center, Nijmegen, the Netherlands;
CHD patients reduce their mortality risk by perform-
and the bResearch Institute for Sports and Exercise Sciences, Liverpool
ing PA volumes below current recommendations. The
a
John Moores University, Liverpool, United Kingdom. Dr. Eijsvogels is supported by a European Commission Horizon 2020 grant (Marie
low volume of this minimal effective dose may
Sklodowska-Curie Fellowship 655502). Dr. Maessen is financially sup-
stimulate patients to incorporate feasible PA goals
ported by an INTERREG VA grant (203072/WP1).
in their daily lives and may also eliminate barriers,
1702
Eijsvogels and Maessen
JACC VOL. 70, NO. 14, 2017 OCTOBER 3, 2017:1701–3
Exercise Prescription for Coronary Heart Disease Patients
such as insufficient time or self-confidence, to
inactive patients (17). Therefore, findings from Stew-
become physically active.
art et al. (8) do not exclude the possibility that
An important limitation of the study by Stewart et al. (8) is that questionnaires were used to assess PA.
Questionnaires,
including
the
extreme PA may worsen cardiovascular outcomes for CHD patients.
International
Regardless of the PA volume, patients who
Physical Activity Questionnaire, overestimate PA
performed any vigorous-intensity PA had a lower
volumes, and there is poor agreement between
mortality risk compared with those performing only
objective (accelerometers) and self-reported PA (9).
low- or moderate-intensity PA. High-intensity inter-
Average PA volume in the present study was 40
val training is also increasingly applied to cardiac
metabolic equivalents (METs) h/week, which is
rehabilitation programs, and a recent meta-analysis
equivalent to 3.5 to 4 current PA recommendations
showed that high-intensity interval training pro-
and can be translated to 10 h of walking per week. It
duces greater increases in cardiopulmonary fitness
is unlikely that the STABILITY patients were so
compared with traditional moderate-intensity exer-
active, because a recent review found that 41 METs
cise training (18). The superior health benefits of
h/week
reduce
vigorous PA have been established in the general
cardiovascular events in the general population (10).
population previously (10,19), and Stewart et al. (8)
A potential explanation for the high PA volumes may
suggest that these findings can be extrapolated to
relate to the inclusion of low-intensity and work-
the CHD community.
is
the
optimal
PA
volume
to
epidemiological
In summary, findings from this large-scale study
studies include moderate to vigorous intensity PA
among CHD patients demonstrate that low volumes
only (11). Nevertheless, we can assume that the
of PA are associated with large risk reductions for
PA-related health benefits start at lower PA volumes
all-cause and cardiovascular mortality. Increasing
related activities, because
most
than those estimated in the present study.
volumes of PA yield additional health benefits, but
The greatest reductions in mortality risk were
the absolute decrease in mortality risk becomes
found in the most active patients. These observations
smaller for every doubling of PA volume. Vigorous
align with dose-response analyses in the general
intensity PA was associated with the lowest mortality
population (11,12) and suggest that high volumes of
risk, suggesting that patients benefit most from this
PA do not increase mortality risks. Although similar
type of exercise. These novel insights inform us about
data were reported in a Norwegian cohort of CHD
effective exercise regimens for secondary prevention,
patients (13), studies in American heart attack survi-
but require confirmation from additional studies.
vors (14) and British (15) and German (16) CHD
In
patients found attenuated health benefits in the most
remember that a little is good, more is better, and
active group. Differences in study methodology and
vigorous is best.
the
interim,
patients
and
clinicians
should
follow-up duration may contribute to these discrepancies. Furthermore, it is important to emphasize
ADDRESS
that patients in the STABILITY trial mainly performed
M.H. Eijsvogels, Department of Physiology (392),
FOR
CORRESPONDENCE:
low- to moderate-intensity PA, whereas vigorous-
Radboud
intensity PA is known to transiently increase the
9101, 6500 HB Nijmegen, the Netherlands. E-mail:
risk for sudden cardiac death, especially in previously
[email protected].
University
Medical
Center,
Dr. P.O.
Thijs Box
REFERENCES 1. Maessen MF, Verbeek AL, Bakker EA, Thompson PD, Hopman MT, Eijsvogels TM. Lifelong exercise patterns and cardiovascular health.
4. Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee Report. Washington DC, U.S.: Department
Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2012;60:e44–164.
Mayo Clin Proc 2016;91:745–54.
of Health and Human Services. 2008. Available at: https://health.gov/paguidelines/report/pdf/ CommitteeReport.pdf Accessed July 27, 2017.
6. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:e78–140.
2. Wen CP, Wai JP, Tsai MK, et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 2011;378: 1244–53. 3. Ekelund U, Steene-Johannessen J, Brown WJ, et al. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. Lancet 2016;388:1302–10.
5. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/ AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for
7. Anderson L, Oldridge N, Thompson DR, et al. Exercise-based cardiac rehabilitation for coronary heart disease: Cochrane systematic review and meta-analysis. J Am Coll Cardiol 2016;67:1–12. 8. Stewart RAH, Held C, Hadziosmanovic N, et al., on behalf of the STABILITY Investigators. Physical
Eijsvogels and Maessen
JACC VOL. 70, NO. 14, 2017 OCTOBER 3, 2017:1701–3
activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol 2017;70: 1689–700. 9. Dyrstad SM, Hansen BH, Holme IM, Anderssen SA. Comparison of self-reported versus accelerometer-measured physical activity. Med Sci Sport Exer 2014;46:99–106. 10. Eijsvogels TM, Molossi S, Lee DC, Emery MS, Thompson PD. Exercise at the extremes: the amount of exercise to reduce cardiovascular events. J Am Coll Cardiol 2016;67: 316–29. 11. Arem H, Moore SC, Patel A, et al. Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA Intern Med 2015;175:959–67.
Exercise Prescription for Coronary Heart Disease Patients
13. Moholdt T, Wisloff U, Nilsen TI, Slordahl SA. Physical activity and mortality in men and women with coronary heart disease: a prospective population-based cohort study in Norway (the HUNT
17. Mittleman MA, Maclure M, Tofler GH, et al., for the Determinants of Myocardial Infarction Onset Study Investigators. Triggering of acute myocardial infarction by heavy physical exertion: protec-
study). Eur J Cardiovasc Prev Rehabil 2008;15: 639–45.
tion against triggering by regular exertion. N Engl J Med 1993;329:1677–83.
14. Williams PT, Thompson PD. Increased cardiovascular disease mortality associated with exces-
18. Elliott AD, Rajopadhyaya K, Bentley DJ, Beltrame JF, Aromataris EC. Interval training versus continuous exercise in patients with coronary artery disease: a meta-analysis. Heart Lung Circ 2015;24:149–57.
sive exercise in heart attack survivors. Mayo Clin Proc 2014;89:1187–94. 15. Wannamethee SG, Shaper AG, Walker M. Physical activity and mortality in older men with diagnosed coronary heart disease. Circulation 2000;102:1358–63.
12. Paffenbarger RS Jr., Hyde RT, Wing AL,
16. Mons U, Hahmann H, Brenner H. A reverse J-shaped association of leisure time physical activity with prognosis in patients with stable coro-
Hsieh CC. Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med 1986;314:605–13.
nary heart disease: evidence from a large cohort with repeated measurements. Heart 2014;100: 1043–9.
19. Gebel K, Ding D, Chey T, Stamatakis E, Brown WJ, Bauman AE. Effect of moderate to vigorous physical activity on all-cause mortality in middle-aged and older Australians. JAMA Intern Med 2015;175:970–7.
KEY WORDS cardiac rehab, cardiorespiratory fitness, exercise training, physical activity, secondary prevention
1703
VOL. 70, NO. 14, 2017
ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jacc.2017.08.016
EDITORIAL COMMENT
Exercise for Coronary Heart Disease Patients Little Is Good, More Is Better, Vigorous Is Best* Thijs M.H. Eijsvogels, PHD,a,b Martijn F.H. Maessen, PHDa
T
he
cardiovascular
health
benefits
of
a
and mortality in 15,486 patients with stable CHD who
physically active lifestyle are well recognized
participated
and frequently described (1,2). Nevertheless,
Atherosclerotic Plaque by Initiation of Darapladib
physical inactivity remains a global problem, particu-
Therapy) trial. Patients from 39 countries were allo-
larly in clinical populations such as coronary heart
cated to tertiles of PA. The intermediate and most
disease
active tertile had a lower risk for all-cause mortality
(CHD) patients. A recent meta-analysis
in
the
STABILITY
(Stabilization
of
including >1,000,000 individuals found that individ-
(hazard ratio [HR]: 0.75; 95% confidence interval [CI]:
uals who are inactive and sit the most have the
0.65 to 0.87, and HR: 0.70; 95% CI: 0.60 to 0.82),
highest risk for mortality (3). The typical CHD patient
cardiovascular mortality (HR: 0.89; 95% CI: 0.74 to
fits this description as she or he usually performs
1.06, and HR: 0.71; 95% CI: 0.58 to 0.88), and non-
little regular exercise and sits much of the time. Stra-
cardiovascular mortality (HR: 0.54; 95% CI: 0.41 to
tegies to increase physical activity (PA) and decrease
0.72, and HR: 0.73; 95% CI: 0.55 to 0.96) compared
sitting in high-risk populations such as CHD patients
with the least active tertile. The most active tertile
are therefore needed. Current guidelines prescribe
also had a lower risk for major adverse coronary
similar PA recommendations for primary (4) and sec-
events (HR: 0.81; 95% CI: 0.71 to 0.92), whereas
ondary prevention (5,6): 150 min/week of exercise at
there were no differences in the risk for myocardial
a moderate intensity. Most evidence for the health
infarction and stroke across all tertiles. The dose-
benefits of exercise in CHD patients are derived
response analysis showed a curvilinear relationship
from cardiac rehab studies (7). Although these find-
between PA and mortality with the largest risk re-
ings support the benefits of regular PA, these studies
ductions at the beginning of the curve. Furthermore,
do not inform on the minimal dose, optimal dose, and
the PA-associated reductions in mortality were greater
potential upper limit of PA to reduce cardiovascular
among CHD patients, whose exercise was limited by
morbidity and mortality.
dyspnea and in those with a high STABILITY CHD risk
SEE PAGE 1689
score, suggesting that high-risk patients benefit the most from a physically active lifestyle.
In this issue of the Journal, Stewart et al. (8)
This study provides important insight in the health
describe the association between self-reported PA
benefits of exercise training and habitual PA in CHD patients. Data from Stewart et al. (8) suggest that as little as 10 min/day of brisk walking (i.e., 3.5 mph) is
*Editorials published in the Journal of the American College of Cardiology
associated with a 33% risk reduction for all-cause
reflect the views of the authors and do not necessarily represent the
mortality. For those unable to walk at a brisk pace,
views of JACC or the American College of Cardiology.
15 to 20 min/day at a slower pace (2 to 2.5 mph) will
From the Radboud Institute for Health Sciences, Department of Physi-
yield similar benefits (8). These findings suggest that
ology, Radboud University Medical Center, Nijmegen, the Netherlands;
CHD patients reduce their mortality risk by perform-
and the bResearch Institute for Sports and Exercise Sciences, Liverpool
ing PA volumes below current recommendations. The
a
John Moores University, Liverpool, United Kingdom. Dr. Eijsvogels is supported by a European Commission Horizon 2020 grant (Marie
low volume of this minimal effective dose may
Sklodowska-Curie Fellowship 655502). Dr. Maessen is financially sup-
stimulate patients to incorporate feasible PA goals
ported by an INTERREG VA grant (203072/WP1).
in their daily lives and may also eliminate barriers,
1702
Eijsvogels and Maessen
JACC VOL. 70, NO. 14, 2017 OCTOBER 3, 2017:1701–3
Exercise Prescription for Coronary Heart Disease Patients
such as insufficient time or self-confidence, to
inactive patients (17). Therefore, findings from Stew-
become physically active.
art et al. (8) do not exclude the possibility that
An important limitation of the study by Stewart et al. (8) is that questionnaires were used to assess PA.
Questionnaires,
including
the
extreme PA may worsen cardiovascular outcomes for CHD patients.
International
Regardless of the PA volume, patients who
Physical Activity Questionnaire, overestimate PA
performed any vigorous-intensity PA had a lower
volumes, and there is poor agreement between
mortality risk compared with those performing only
objective (accelerometers) and self-reported PA (9).
low- or moderate-intensity PA. High-intensity inter-
Average PA volume in the present study was 40
val training is also increasingly applied to cardiac
metabolic equivalents (METs) h/week, which is
rehabilitation programs, and a recent meta-analysis
equivalent to 3.5 to 4 current PA recommendations
showed that high-intensity interval training pro-
and can be translated to 10 h of walking per week. It
duces greater increases in cardiopulmonary fitness
is unlikely that the STABILITY patients were so
compared with traditional moderate-intensity exer-
active, because a recent review found that 41 METs
cise training (18). The superior health benefits of
h/week
reduce
vigorous PA have been established in the general
cardiovascular events in the general population (10).
population previously (10,19), and Stewart et al. (8)
A potential explanation for the high PA volumes may
suggest that these findings can be extrapolated to
relate to the inclusion of low-intensity and work-
the CHD community.
is
the
optimal
PA
volume
to
epidemiological
In summary, findings from this large-scale study
studies include moderate to vigorous intensity PA
among CHD patients demonstrate that low volumes
only (11). Nevertheless, we can assume that the
of PA are associated with large risk reductions for
PA-related health benefits start at lower PA volumes
all-cause and cardiovascular mortality. Increasing
related activities, because
most
than those estimated in the present study.
volumes of PA yield additional health benefits, but
The greatest reductions in mortality risk were
the absolute decrease in mortality risk becomes
found in the most active patients. These observations
smaller for every doubling of PA volume. Vigorous
align with dose-response analyses in the general
intensity PA was associated with the lowest mortality
population (11,12) and suggest that high volumes of
risk, suggesting that patients benefit most from this
PA do not increase mortality risks. Although similar
type of exercise. These novel insights inform us about
data were reported in a Norwegian cohort of CHD
effective exercise regimens for secondary prevention,
patients (13), studies in American heart attack survi-
but require confirmation from additional studies.
vors (14) and British (15) and German (16) CHD
In
patients found attenuated health benefits in the most
remember that a little is good, more is better, and
active group. Differences in study methodology and
vigorous is best.
the
interim,
patients
and
clinicians
should
follow-up duration may contribute to these discrepancies. Furthermore, it is important to emphasize
ADDRESS
that patients in the STABILITY trial mainly performed
M.H. Eijsvogels, Department of Physiology (392),
FOR
CORRESPONDENCE:
low- to moderate-intensity PA, whereas vigorous-
Radboud
intensity PA is known to transiently increase the
9101, 6500 HB Nijmegen, the Netherlands. E-mail:
risk for sudden cardiac death, especially in previously
[email protected].
University
Medical
Center,
Dr. P.O.
Thijs Box
REFERENCES 1. Maessen MF, Verbeek AL, Bakker EA, Thompson PD, Hopman MT, Eijsvogels TM. Lifelong exercise patterns and cardiovascular health.
4. Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee Report. Washington DC, U.S.: Department
Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2012;60:e44–164.
Mayo Clin Proc 2016;91:745–54.
of Health and Human Services. 2008. Available at: https://health.gov/paguidelines/report/pdf/ CommitteeReport.pdf Accessed July 27, 2017.
6. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;61:e78–140.
2. Wen CP, Wai JP, Tsai MK, et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 2011;378: 1244–53. 3. Ekelund U, Steene-Johannessen J, Brown WJ, et al. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. Lancet 2016;388:1302–10.
5. Fihn SD, Gardin JM, Abrams J, et al. 2012 ACCF/ AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for
7. Anderson L, Oldridge N, Thompson DR, et al. Exercise-based cardiac rehabilitation for coronary heart disease: Cochrane systematic review and meta-analysis. J Am Coll Cardiol 2016;67:1–12. 8. Stewart RAH, Held C, Hadziosmanovic N, et al., on behalf of the STABILITY Investigators. Physical
Eijsvogels and Maessen
JACC VOL. 70, NO. 14, 2017 OCTOBER 3, 2017:1701–3
activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol 2017;70: 1689–700. 9. Dyrstad SM, Hansen BH, Holme IM, Anderssen SA. Comparison of self-reported versus accelerometer-measured physical activity. Med Sci Sport Exer 2014;46:99–106. 10. Eijsvogels TM, Molossi S, Lee DC, Emery MS, Thompson PD. Exercise at the extremes: the amount of exercise to reduce cardiovascular events. J Am Coll Cardiol 2016;67: 316–29. 11. Arem H, Moore SC, Patel A, et al. Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA Intern Med 2015;175:959–67.
Exercise Prescription for Coronary Heart Disease Patients
13. Moholdt T, Wisloff U, Nilsen TI, Slordahl SA. Physical activity and mortality in men and women with coronary heart disease: a prospective population-based cohort study in Norway (the HUNT
17. Mittleman MA, Maclure M, Tofler GH, et al., for the Determinants of Myocardial Infarction Onset Study Investigators. Triggering of acute myocardial infarction by heavy physical exertion: protec-
study). Eur J Cardiovasc Prev Rehabil 2008;15: 639–45.
tion against triggering by regular exertion. N Engl J Med 1993;329:1677–83.
14. Williams PT, Thompson PD. Increased cardiovascular disease mortality associated with exces-
18. Elliott AD, Rajopadhyaya K, Bentley DJ, Beltrame JF, Aromataris EC. Interval training versus continuous exercise in patients with coronary artery disease: a meta-analysis. Heart Lung Circ 2015;24:149–57.
sive exercise in heart attack survivors. Mayo Clin Proc 2014;89:1187–94. 15. Wannamethee SG, Shaper AG, Walker M. Physical activity and mortality in older men with diagnosed coronary heart disease. Circulation 2000;102:1358–63.
12. Paffenbarger RS Jr., Hyde RT, Wing AL,
16. Mons U, Hahmann H, Brenner H. A reverse J-shaped association of leisure time physical activity with prognosis in patients with stable coro-
Hsieh CC. Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med 1986;314:605–13.
nary heart disease: evidence from a large cohort with repeated measurements. Heart 2014;100: 1043–9.
19. Gebel K, Ding D, Chey T, Stamatakis E, Brown WJ, Bauman AE. Effect of moderate to vigorous physical activity on all-cause mortality in middle-aged and older Australians. JAMA Intern Med 2015;175:970–7.
KEY WORDS cardiac rehab, cardiorespiratory fitness, exercise training, physical activity, secondary prevention
1703