The Ne w E n g l a nd Jo ur n a l o f Me d ic i ne
Review Article
Medical Progress
CARDIAC REHABILITATION AND
SECONDARY PREVENTION OF
CORONARY HEART DISEASE
PHILIP A. ADES, M.D.
C
ORONARY heart disease is the leading cause
of death in the United States among men
and women.1 It is also a major cause of phys-
ical disability, particularly in the rapidly growing pop-
ulation of elderly persons.2,3 In 1997, acute myocardial
infarction was diagnosed in 1.1 million Americans,
and 800,000 patients underwent coronary revascu-
larization.1 The prevention of subsequent coronary
events and the maintenance of physical functioning in
such patients are major challenges in preventive care.
Cardiac-rehabilitation programs were first developed
in the 1960s,4-6 once the benefits of ambulation dur-
ing prolonged hospitalization for coronary events had
been recognized.7 After discharge from the hospital,
the process of physical reconditioning was continued
at home. Concern about the safety of unsupervised ex-
ercise after discharge led to the development of highly
structured rehabilitation programs that were super-
vised by physicians and included electrocardiographic
monitoring. The focus of these programs was almost
exclusively on exercise.
The hospital stay for acute coronary syndromes
has now been shortened to three to five days so that
deconditioning is minimal.8 With shorter stays, how-
ever, the opportunity to counsel patients about risk re-
duction and exercise is diminished. There is convinc-
ing evidence that regular exercise and modification
of risk factors favorably alter the clinical course of
coronary heart disease.9-13 Clinical practice guidelines,
sponsored jointly by the Agency for Health Care
Policy and Research and the National Institutes of
Health, have broadened the scope of cardiac-rehabil-
itation programs to include the assessment and mod-
ification of risk factors, so that these programs func-
tion as secondary-prevention centers.14
The benefits of cardiac rehabilitation and second-
From the Department of Medicine, Division of Cardiology, University
of Vermont College of Medicine and Fletcher Allen Health Care, Burling-
ton. Address reprint requests to Dr. Ades at McClure 1, Cardiology, Fletch-
er Allen Health Care, MCHV Campus, Burlington, VT 05401, or at
philip.ades@vtmednet.org.
892 · N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org
Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .
Copyright © 2001 Massachusetts Medical Society. All rights reserved.
ary prevention are broad and compelling. Controlled
trials of exercise after myocardial infarction, reported
in the 1980s, have demonstrated reductions in over-
all mortality and in mortality from cardiovascular
causes.9,10 Trials of exercise combined with nutritional
counseling have demonstrated a slowing of the athero-
sclerotic process12,13,15,16 and decreased rates of subse-
quent coronary events and hospitalization.11,13 Despite
the well-established benefits of exercise and nutrition-
al counseling, physicians are generally not well trained,
and do not have the time to provide effective nutri-
tional advice, guidance about weight management,
and a prescription for exercise. The provision of all
these services at cardiac-rehabilitation centers, with
the use of well-established algorithms to set goals for
risk reduction17,18 and in coordination with the pri-
mary care physician, is efficient and effective.
Only 10 to 20 percent of appropriate candidates
in the United States currently participate in formal
rehabilitation programs.14,19 The reasons for low par-
ticipation rates include the geographic maldistribu-
tion of available programs and the failure of physi-
cians to refer patients, particularly elderly persons and
women, to the programs.20,21 Home-base rehabilita-
tion programs that are directed by physicians and
coordinated by nurses have been developed as a way
of expanding the delivery of secondary-prevention
services.13,22,23
Cardiac rehabilitation is indicated for patients who
have received a diagnosis of acute myocardial infarc-
tion, those who have undergone coronary revascu-
larization, and those with chronic stable angina. It is
also appropriate for patients with chronic heart failure
and those who have undergone cardiac transplanta-
tion. The goals of cardiac rehabilitation and secondary
prevention are to prevent disability resulting from cor-
onary disease, particularly in elderly persons and those
with occupations that involve physical exertion, and to
prevent subsequent coronary events, subsequent hos-
pitalization, and death from cardiac causes through
a program of prescribed exercise and interventions
designed to modify coronary risk factors, including
drug therapy.
EXERCISE INTOLERANCE AND DISABILITY
IN PATIENTS WITH CORONARY
HEART DISEASE
The cardinal symptoms of coronary heart disease,
angina and exertional dyspnea, reflect a complex inter-
play of abnormalities of vascular function and cardiac
hemodynamics, compounded by physical decondi-
tioning and psychological factors. Angina pectoris
and ischemic left ventricular dysfunction result from
 MED ICA L PR OGR ES S
an imbalance between the supply of and the demand
for myocardial oxygen. In the presence of coronary
atherosclerosis, exercise-induced increases in blood
flow are limited both by atheroma and by an abnor-
mal vascular endothelial response that paradoxically
results in vasoconstriction on exertion.24,25 Abnor-
malities of left ventricular diastolic inflow, which are
particularly common in older patients with coronary
heart disease, also lead to exertional dyspnea, which
may limit the capacity for exercise.26 Finally, patients
with coronary heart disease frequently limit their phys-
ical activities because of the fear of adverse conse-
quences, resulting in a cycle of inactivity and decon-
ditioning.27
Among middle-aged and older persons, those with
coronary heart disease have higher rates of self-report-
ed physical disability, as defined by a diminished ability
to perform activities of daily living, than do persons
without coronary heart disease 2,28 (Fig. 1). Older age,
female sex, and clinical manifestations of angina pec-
toris or chronic heart failure are associated with the
highest rates of disability.2 Other factors associated
with disability include a low level of aerobic fitness,
a high score for depression, and diminished muscular
strength.29 However, a patient’s perceived inability to
perform an activity is not necessarily correlated with
actual physical incapacity. More than a quarter of pa-
tients with coronary heart disease terminate an exer-
cise stress test before attaining a true physiologic
maximal effort, in the absence of coronary ischemia,
heart failure, or arrhythmias, and elderly persons have
the highest rates of early termination.27,30 Providing
patients with information about the safety of specific
physical activities minimizes the perception of phys-
ical limitation that results in disability.
EXERCISE TRAINING
Safety
Rates of coronary events in rehabilitation settings
have been exceedingly low. A survey of 167 super-
vised programs showed that the rate of cardiac arrest
was 1 per 112,000 patient-hours and the rate of non-
fatal myocardial infarction was 1 per 294,000 patient-
hours; the mortality rate was 1 per 784,000 patient-
hours.31 Despite the recent inclusion in such programs
of patients at increased risk of adverse events, such as
patients with chronic heart failure, older patients, and
heart-transplant recipients, the rate of adverse events
has not increased appreciably.32
Effects on Exercise Tolerance, Symptoms,
and Coronary Events
Exercise capacity consistently improves after cardiac
rehabilitation. After three months of aerobic condi-
tioning three times a week at an intensity of 70 to
85 percent of the maximal heart rate, exercise toler-
ance on the treadmill increases by 30 to 50 percent,
and peak oxygen consumption increases by 15 to 20
N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org · 893
Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .
Copyright © 2001 Massachusetts Medical Society. All rights reserved.
percent.14 Patient-reported activities of daily living,
such as climbing stairs and carrying groceries, also
improve.33 Among patients with angina, the pain
threshold increases and the angina often resolves be-
cause the product of the heart rate and systolic pres-
sure is reduced during exercise, a physiologic byprod-
uct of exercise training.34,35
Physiologic adaptations to aerobic conditioning in
patients with coronary heart disease include central
(cardiac) and peripheral (skeletal-muscle and vascular)
adaptations resulting in a widened difference in ox-
ygen content between arterial and venous blood dur-
ing maximal exercise and an increased capacity to
deliver substrate to skeletal and cardiac muscle.36,37
Cardiac adaptations include increases in cardiac di-
mensions, stroke work, cardiac output, and afterload-
corrected indexes of left ventricular function.37,38 Skel-
etal-muscle adaptations include an increase in fiber
area and in oxidative-enzyme activity.37 Vascular ad-
aptations include an increase in the density of skele-
tal-muscle capillaries and improvements in endothe-
lial-dependent vasodilatation in both epicardial and
resistance coronary arteries.24
Meta-analyses of 21 randomized, controlled trials
performed in the 1970s and 1980s, involving a total
of more than 4000 patients, provided data on the ef-
fect of cardiac rehabilitation on long-term mortality
from cardiovascular causes and from all causes. Car-
diac rehabilitation was associated with a 25 percent
reduction in overall mortality and mortality from
cardiovascular causes at three years.9,10 More than 80
percent of the patients in these studies were men, and
most of the patients were 65 years of age or younger.
The studies were performed before the widespread
use of thrombolytic therapy, coronary-stent place-
ment, treatment with angiotensin-converting–enzyme
inhibitors, and aggressive lipid-lowering therapy. The
mechanism of the exercise-related decreases in mor-
tality from cardiovascular disease is probably multi-
factorial. Favorable lipid effects,39,40 improvements in
endothelium-mediated coronary vasodilatation,24,41
changes in body composition,40 increased heart-rate
variability and autonomic tone,42 increased fibrinol-
ysis,43,44 and improvements in psychological fac-
tors45,46 may all play a part. The value of exercise train-
ing in patients who are 65 years of age or older is
supported by a recent study involving 772 men with
coronary heart disease, in which physical activity —
in particular, walking for a total of at least four hours
per week — was associated with a significant reduc-
tion in overall mortality.47 However, it has not been
determined whether a cardiac-rehabilitation program
that consists of exercise alone reduces mortality in
current patient populations.
Patients with chronic heart failure have dyspnea and
fatigue, which result in severe exercise intolerance,
and such patients are at highest risk for death, with
a mortality rate at five years that approaches 50 per-
 The Ne w E n g l a nd Jo ur n a l o f Me d ic i ne

100

Persons with Disability (%)

With CHD3
Without CHD 79%
80
64%
60 56%
49% 49%

40
25% 27%

20
9%

0
Men Women Men Women
50–69 Yr 70–88 Yr
Figure 1. Rates of Disability According to Age, Sex, and the Presence or Absence of Coronary Heart
Disease (CHD).
Data are from the Framingham Disability Study.2 P<0.001 for the comparison between persons of ei-
ther sex with CHD and those without CHD in each age group and for the comparison between women
and men in each age group, regardless of the presence or absence of CHD. P<0.05 for the comparisons
between older persons with CHD and younger persons with CHD and between older and younger per-
sons without CHD.

cent.48 Because the incidence of heart failure rises sub-
stantially after the age of 65 years, its prevalence is
increasing as the population ages.48 Aerobic condi-
tioning results in improvements in exercise capacity,49
neurohumoral abnormalities,50 autonomic tone,50 and
mitochondrial oxidative-enzyme activity in skeletal
muscle.51 In a randomized, controlled trial, moderate-
ly intense aerobic exercise for one year improved pa-
tient-reported measures of the quality of life and re-
duced overall mortality and hospital-readmission
rates.52 In a study involving 68 patients awaiting car-
diac transplantation, exercise tolerance improved suf-
ficiently after cardiac rehabilitation for 31 of the pa-
tients to be removed from the waiting list for a
transplant.53 After cardiac transplantation, regular ex-
ercise training increases both work capacity and max-
imal aerobic capacity.54 In summary, exercise improves
functional capacity and decreases symptoms in pa-
tients with coronary heart disease or chronic heart fail-
ure, in addition to decreasing overall mortality and
mortality from cardiovascular disease.
Effects on Coronary Risk Factors
Cardiac rehabilitation in the form of exercise
alone, without intensive nutritional counseling, has
favorable, though not pronounced, effects on coro-
nary risk factors. The most consistent effects on lip-
ids are an increase of 8 to 23 percent in high-density
lipoprotein (HDL) cholesterol and an increase of 5 to
26 percent in the ratio of total cholesterol to HDL
cholesterol.39,40,55 The increases in HDL cholesterol
are similar to those associated with drug therapy.56
To put these findings in perspective, a 7.5 percent in-
crease in HDL cholesterol with gemfibrozil yielded
a 22 percent decrease in the risk of myocardial infarc-
tion or death from cardiac causes over a period of
five years.56 For patients with base-line triglyceride
values that exceed 200 mg per deciliter (2.26 mmol
per liter), exercise alone, without dietary change, de-
creases triglyceride levels by 22 percent.40 The mini-
mal effect of exercise training alone on low-density lip-
oprotein (LDL) cholesterol makes a strong case for
concurrent nutritional counseling and drug therapy.40
The effects of exercise alone on excess weight and
insulin resistance are minimal to moderate. A cardiac-
rehabilitation program consisting of exercise alone is
associated with a 0 to 2 percent change in body weight
at three months,40,57 although fat mass decreases by
5 percent, along with a 2 percent increase in muscle
mass.40 A three-week period of exercise training in
patients with coronary heart disease is associated with
improved glucose metabolism and diminished insu-
lin resistance.58
Prescription of Exercise
Prescribed exercise for patients with coronary heart
disease has evolved from standard regimens for all
patients to individualized regimens based on the clin-
ical profile of the patient, including risk factors, age,
and functional status (Table 1). Historically, walking
and use of a bicycle ergometer have been the preferred
forms of exercise, with sessions performed at mod-
erate-to-high intensity (65 to 85 percent of the max-
imal measured heart rate) two to four times a week
for 30 to 45 minutes per session. The low caloric ex-
penditure of this exercise regimen — approximately

894 · N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org

Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .

Copyright © 2001 Massachusetts Medical Society. All rights reserved.
 MED IC A L PR OGR ES S
TABLE 1. EXERCISE PRESCRIPTION ACCORDING
CHARACTERISTIC TRAINING REGIMEN INTENSITY
Age <65 yr, not over- High-intensity aerobic 75–85% of maximal
weight heart rate
Age »65 yr Low-intensity aerobic 65–75% of maximal
and resistance heart rate
Overweight Aerobic — high caloric 65–80% of maximal
expenditure heart rate
Age >65 yr and disabled, Resistance 50–75% of single-
engaged in physical repetition maxi-
work, or overweight mal lift
270 to 283 kcal per session59,60 — may explain its
minimal effects on body weight and cardiac risk fac-
tors. More than 75 percent of candidates for cardiac
rehabilitation are overweight, defined as a body-mass
index (the weight in kilograms divided by the square
of the height in meters) that exceeds 25.61 Maximi-
zation of the total exercise-related caloric expendi-
ture is necessary to reduce weight and improve risk
factors related to excess weight (hyperlipidemia, in-
sulin resistance, and hypertension). Preliminary data
suggest that a regimen of low-intensity, prolonged,
daily exercise, called “high caloric training” because
it maximizes the expenditure of calories, results in
greater fat loss and a greater modification of risk fac-
tors than does a regimen of more intense but briefer
exercise sessions.62 Resistance training should be in-
cluded in the exercise prescription to minimize loss
of muscle mass.
The general cardioprotective effects of exercise in
patients with coronary heart disease may be due to its
effects on the coronary endothelium. A regimen of
six daily, 10-minute sessions on a bicycle ergometer,
at an intensity of 80 percent of the maximal measured
heart rate, is associated with an improvement in endo-
thelium-dependent vasodilatation of coronary arteries
after four weeks.24 Thus, repeated, short sessions of
relatively intense exercise (“interval training”) should
often be part of the exercise prescription.
Over 50 percent of candidates for cardiac rehabil-
itation are over the age of 65 years. A primary goal of
rehabilitation in such patients, many of whom have
coexisting disorders and severe deconditioning, is to
prevent or minimize disability. Exercise training begins
with multiple sessions of low-intensity exercise, with
a gradual increase in the duration of the sessions.
Resistance training is particularly important in older
patients, especially women, a subgroup in which dis-
ability rates are extremely high and muscular strength
is often a limiting factor.2,33,63 Numerous studies have
N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org · 895
Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .
Copyright © 2001 Massachusetts Medical Society. All rights reserved.
TO THE CHARACTERISTICS OF THE PATIENT.
FREQUENCY DURATION OF
TYPE OF EXERCISE OFSESSIONS EACH SESSION
no./wk min
Walking, jogging, cycling, rowing 3 or 4 30–45 (continuous or
interval)
Walking, cycling, rowing 3 or 4 30 (may be intermittent)
Walking 5 or 6 45–60
Weight machine and dumbbells, 2 or 3 10–20 (10 repetitions
with the focus on upper legs, of each of 5 to 7 exer-
shoulders, and arms cises)
documented the safety and efficacy of aerobic and
resistance training for older patients with coronary
heart disease.64-67 In summary, the clinician should tai-
lor the exercise regimen to the clinical characteristics
of the patient, recognizing that certain benefits of ex-
ercise, such as increases in functional capacity and
HDL cholesterol and improvement in the coronary
vasodilator response, occur in all patients with cor-
onary heart disease (Table 2).
The following two case vignettes illustrate the in-
dividualized prescription of exercise in the practice
of cardiac rehabilitation.
Case 1
A 50-year-old man was referred for cardiac reha-
bilitation, including modification of coronary risk
factors and guidance about returning to work, three
weeks after an acute myocardial infarction. Coronary
risk factors included obesity, dyslipidemia, and type 2
diabetes. The patient was employed as a construction
worker. His hospitalization had been uncomplicated,
and he had been discharged after four days. On exer-
cise testing two weeks later, he attained a high work-
load at a heart rate of 140 beats per minute, without
angina or electrocardiographic evidence of ischemic
changes.
The goals of cardiac rehabilitation for this patient
were loss of weight, with its attendant favorable ef-
fects on dyslipidemia and type 2 diabetes, and a safe
and timely return to work. The patient was told that
long daily walks at a slow-to-moderate pace would
maximize his caloric expenditure and facilitate weight
loss. In addition, supervised resistance training was
recommended to maintain muscle mass and strength,
and thus foster the patient’s confidence in perform-
ing heavy physical labor. Daily sessions of walking at
a heart rate of up to 112 beats per minute (80 per-
cent of the maximal heart rate during exercise), with
a progression from 30 minutes per day to 45 to 60
 The Ne w E n g l a nd Jo ur n a l o f Me d ic i ne

TABLE 2. COMPONENTS OF CARDIAC REHABILITATION AND ASSOCIATED GOALS.*

Initial evaluation
Take medical history and perform physical examination
Measure risk factors
Obtain electrocardiograms at rest and during exercise
Provide vocational counseling
Determine level of risk
Goal: formulation of preventive plan in collaboration with primary care physician
Management of lipid levels
Assess and modify diet, physical activity, and drug therapy
Primary goal: LDL cholesterol level <100 mg/dl
Secondary goals: HDL cholesterol level >45 mg/dl, triglyceride level <200 mg/dl
Management of hypertension
Measure blood pressure frequently at rest and during exercise
If resting systolic pressure is 130–139 mm Hg or diastolic pressure is 85–89 mm Hg, recommend lifestyle modifications,
including exercise, weight management, sodium restriction, and moderation of alcohol intake; if patient has diabetes
or chronic renal or heart failure, consider drug therapy
If resting systolic pressure is »140 mm Hg or diastolic pressure is »90 mm Hg, recommend drug therapy
Monitor effects of intervention in collaboration with primary care physician
Goal: blood pressure <140/90 mm Hg (or <130/85 mm Hg if patient has diabetes or chronic heart or renal failure)
Cessation of smoking
Document smoking status (never smoked, stopped smoking in remote past, stopped smoking recently, or currently
smokes)
Determine patient’s readiness to quit; if ready, pick date
Offer nicotine-replacement therapy, bupropion, or both
Offer behavioral advice and group or individual counseling
Goal: long-term abstinence
Weight reduction
Consider for patients with BMI >25 or waist circumference >100 cm (in men) or >90 cm (in women), particularly if
associated with hypertension, hyperlipidemia, or insulin resistance or diabetes
Provide behavioral and nutritional counseling with follow-up to monitor progress in achieving goals
Goals: loss of 5–10% of body weight and modification of associated risk factors
Management of diabetes
Identify candidates on the basis of the medical history and base-line glucose test
Develop a regimen of dietary modification, weight control, and exercise combined with oral hypoglycemic agents and
insulin therapy
Monitor glucose control before and after exercise sessions and communicate results to primary care physician
For newly detected diabetes, refer patient to primary care physician for evaluation and treatment
Goals: normalization of fasting plasma glucose level (80–110 mg/dl) or glycosylated hemoglobin level (<7.0%) and con-
trol of associated obesity, hypertension, and hyperlipidemia
Psychosocial management
Identify psychosocial problems such as depression, anxiety, social isolation, anger, and hostility by means of an interview,
standardized questionnaires, or both
Provide individual or group counseling, or both, for patients with clinically significant psychosocial problems
Provide stress-reduction classes for all patients
Goal: absence of clinically significant psychosocial problems and acquisition of stress-management skills
Physical-activity counseling and exercise training
Assess current physical activity and exercise tolerance with monitored exercise stress test
Identify barriers to increased physical activity
Provide advice regarding increasing physical activity
Develop an individualized regimen of aerobic and resistance training, specifying frequency, intensity, duration, and types
of exercise
Goals: increases in regular physical activity, strength, and physical functioning, expenditure of at least 1000 kcal per week
in physical activity

*Adapted from Balady et al.17 The body-mass index (BMI) is the weight in kilograms divided by the square of the
height in meters. To convert the values for low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol
to millimoles per liter, multiply by 0.02586. To convert the value for triglycerides to millimoles per liter, multiply by
0.01129. To convert the values for glucose to millimoles per liter, multiply by 0.05551.

minutes per day, were prescribed, and the patient was
encouraged to keep an exercise diary. He also re-
ceived nutritional counseling. The prescribed regimen
of resistance training (sessions performed three days
per week at an intensity of 75 percent of the maximal
weight that he could lift once [a single-repetition
maximal lift]) focused on the muscle groups involved
in work-related activities. A return to work was rec-
ommended after a supervised simulation of the pa-
tient’s customary work had shown that he could per-
form it safely, without angina or electrocardiographic
abnormalities.

896 · N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org

Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .

Copyright © 2001 Massachusetts Medical Society. All rights reserved.
 MED IC A L PR OGR ES S
After three months of center- and home-based ex-
ercise, the patient had lost 6 kg of body weight, and
the weight loss was associated with improvements in
lipid levels and diabetic control. He returned to work
on a half-time schedule six weeks after his infarction
and resumed full-time work two weeks later. The pa-
tient was encouraged to adhere to a long-term, home-
based walking program, and follow-up was arranged.
Case 2
An 85-year-old woman with stable chronic heart
failure and coronary heart disease was referred for car-
diac rehabilitation. Her primary symptoms were dysp-
nea on exertion and difficulty performing household
activities due to lack of strength and stamina. Asso-
ciated chronic illnesses included osteoarthritis, osteo-
porosis, macular degeneration, and esophageal disease.
On a base-line treadmill test, the patient walked for
two minutes at 1.5 mi (2.4 km) per hour and stopped
because of leg fatigue, without angina or electrocar-
diographic evidence of ischemic changes, at a heart
rate of 120 beats per minute.
The goals of cardiac rehabilitation for this patient
were to increase her strength and endurance and to
improve her functioning at home. The patient attend-
ed supervised, on-site rehabilitation sessions once a
week, combined with a home exercise program. The
center-based program included intermittent walking
on a treadmill and resistance training. Treadmill walk-
ing was initiated at a low intensity (two five-minute
sessions at 1.2 mi [1.9 km] per hour) with a gradual
increase in the duration of each session, at a heart
rate of no more than 90 beats per minute (75 percent
of the maximal heart rate during exercise). The resist-
ance training began with two weeks of range-of-
motion exercises involving the use of rubber tubing,
with measurement of the single-repetition maximal
lift for the leg-extension and bench-press exercises.
The intensity of the resistance training was set at 50
percent of the single repetition maximal lift, with
close supervision to prevent excessive straining. Ex-
ercises included the leg extension, bench press, bi-
ceps curl, shoulder press, and leg press. The home-
based exercise program consisted of multiple daily
sessions of stair climbing along with resistance exer-
cises performed every other day with the use of small
dumbbells and a canvas bag loaded with sandbags that
approximated the intensity of the center-based resist-
ance training. The patient kept a detailed diary of ex-
ercise, which was reviewed weekly.
After six months of training, the patient’s leg
strength had increased by 50 percent and her hand-
grip strength had increased by 15 percent. Walking
endurance had increased from two to four minutes
at 2.0 mi (3.2 km) per hour on treadmill testing, and
the patient reported an improved ability to perform
activities of daily living. Long-term exercise was en-
couraged, and follow-up arranged.
N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org · 897
Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .
Copyright © 2001 Massachusetts Medical Society. All rights reserved.
Compliance
The rate of compliance with an exercise regimen
for cardiac rehabilitation is approximately 50 percent
at one year,68,69 as compared with compliance rates
of 64 percent for antihypertensive medication 70 and
82 percent for lipid-lowering agents.71 Several inter-
ventions have been shown to optimize compliance
with an exercise regimen. In one study, a rehabilita-
tion program that included a gradual transition from
supervised, center-based exercise sessions to sessions
performed at home with self-monitoring resulted in
a compliance rate of 92 percent at six months, as com-
pared with a rate of 76 percent for a program that
did not include such a transition.72 The use of low-
intensity exercise,73 nurse case managers,13,22 and the
patient’s written, signed agreement to follow the pre-
scribed regimen74 have also been associated with in-
creased long-term compliance.
COMPREHENSIVE RISK REDUCTION
Secondary prevention focuses on risk reduction in
patients with established coronary heart disease who
are at high risk for recurrent cardiac events and death
from cardiac causes.75 Exercise is only one compo-
nent of such a program; nutritional counseling, be-
havioral interventions, and drug therapy have equally
important roles. The risk-reduction program is com-
monly initiated during hospitalization for a first cor-
onary event (Fig. 2). The cardiac-rehabilitation or
preventive-cardiology nurse immediately initiates ef-
forts to help the patient abstain from smoking.76 Nu-
tritional counseling and behavioral interventions are
also initiated in the hospital to maintain abstinence
from smoking, lower blood lipid levels, control weight
and blood pressure, and manage psychological symp-
toms. With the shortening of hospitalization for cor-
onary events,8 much of the behavioral intervention
has been shifted to the outpatient setting.
Smoking
Cessation of smoking in patients with coronary
heart disease is associated with a marked reduction in
the rate of coronary events.77,78 Among patients with
myocardial infarction, mortality and reinfarction rates
are reduced by 50 percent one year after the cessation
of smoking.77 The best results have been obtained
with a strong recommendation by the physician to
stop smoking combined with interventions managed
by a nurse during the index hospitalization.76 The goal
is to prevent a relapse after discharge, since patients
cannot smoke in the hospital. The interventions in-
clude teaching the patient behavioral skills for coping
with high-risk situations, providing relaxation train-
ing, selectively prescribing bupropion or providing
nicotine supplements (or both), and maintaining pe-
riodic, long-term telephone contact with the patient.
In one study, the rate of smoking cessation one year
after myocardial infarction was 61 percent among
 The Ne w E n g l a nd Jo ur n a l o f Me d ic i ne

Inpatient Outpatient

IdentificationŁ PrescribedŁ Modification ofŁ Specification ofŁ

of Patient Evaluation Exercise Risk Factors Long-Term Goals
Smoking cessationŁ Medical history3 Aerobic training3 Education3 Physical3
and preventionŁ Assessment of riskŁ (high caloric3 NutritionalŁ Vocational3
of relapse3 factors3 or interval)3 counseling3 Psychological3
Initial assessment ofŁ Exercise stress test3 Resistance training3 Exercise3 Clinical
physical activity3 VocationalŁ On-site or at-homeŁ Medication
Outpatient referral counseling exercise program

Figure 2. Elements of Cardiac Rehabilitation.

patients assigned to these interventions but only 32
percent among controls.76
Dyslipidemia
Normalizing blood lipids, according to the values
recommended by the National Cholesterol Education
Program, results in a marked reduction in the rate of
clinical coronary events and mortality in patients with
coronary heart disease. Diverse clinical trials, many of
which used quantitative coronary angiography, have
demonstrated the efficacy of lipid normalization
through medication, diet, and exercise in slowing the
progression of angiographic measures of atherosclero-
sis and in reducing the rate of coronary events.11-13,79-82
In the Scandinavian Simvastatin Survival Study, the
rates of overall mortality and major coronary events
were reduced by 30 and 34 percent, respectively, with
a 35 percent decrease in the mean (±SD) LDL cho-
lesterol level from a base-line value of 256±25 mg
per deciliter (6.6±0.6 mmol per liter).79 In the Cho-
lesterol and Recurrent Events Trial, which enrolled pa-
tients with less pronounced LDL cholesterol eleva-
tions, treatment with pravastatin was associated with a
24 percent reduction in the risk of coronary events.81
In a study involving patients with coronary heart dis-
ease and low levels of HDL cholesterol (40 mg per
deciliter [1.0 mmol per liter] or less), treatment with
gemfibrozil resulted in a 22 percent reduction in the
relative risk of nonfatal myocardial infarction or death
from a cardiac cause.56 Thus, diet, exercise, and drugs
are all indicated to achieve LDL cholesterol levels be-
low 100 mg per deciliter (2.6 mmol per liter), HDL
cholesterol levels above 40 mg per deciliter, and tri-
glyceride values below 200 mg per deciliter.83
Recent studies have shown that in clinical practice,
the goal of reducing the LDL cholesterol level to less
than 100 mg per deciliter is met in less than a third of
patients with coronary heart disease.84,85 This goal is
most likely to be achieved through a systematic ap-
proach to lipid measurement and therapy.13,86,87 Meas-
urement of lipid levels at enrollment in a cardiac-
rehabilitation program and subsequently at regular
intervals, with aggressive lipid-lowering therapy, in
consultation with the primary care physician, triples
the use of drug therapy and significantly reduces LDL
cholesterol levels.87 It is imperative that cardiac-reha-
bilitation programs measure lipid values systematical-
ly, participate actively in therapy, and provide nutri-
tional counseling. Clinicians who provide cardiac
rehabilitation should know the expected effects of ex-
ercise training on lipid levels40 and be familiar with
lipid-normalizing agents. In addition, there should be
ongoing communication with the referring physician.
Excess Weight
The combination of dietary intervention and exer-
cise results in a 4 to 9 percent reduction in the body-
mass index.12,13,15,88 Exercise alone, without individ-
ualized nutritional counseling, has been less successful
in achieving a substantial reduction in weight.61 When
weight loss is accomplished, it is associated with im-
provements in lipid levels, insulin resistance, blood
pressure, and clotting abnormalities.57,89,90 Weight loss
as part of cardiac rehabilitation is not a passive process;
an associated program of behavioral modification is
used as appropriate.91,92 The intervention includes be-
havioral concepts of stimulus control, self-monitoring,
problem solving, social support, and a daily calorie
count. The goal is not to reach the ideal body weight
but rather to achieve improvements in obesity-related
risk factors. In many cases, a sustained loss of 5 to
10 percent of body weight substantially improves risk
factors such as dyslipidemia and insulin resistance.93
An advantage of a weight-reduction program that is
part of an overall program of cardiac rehabilitation
is that the patient is already performing the requisite
exercise component.
Hypertension and Diabetes
The beneficial effects of exercise training, weight
reduction, and dietary modification on blood-pres-
sure control and type 2 diabetes are well known.94-96
Studies in the cardiac-rehabilitation setting are com-
plicated by ongoing drug therapy for patients with
these conditions and by the need for frequent dose
adjustments. For example, doses of oral hypoglyce-

898 · N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org

Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .

Copyright © 2001 Massachusetts Medical Society. All rights reserved.
 MED IC A L PR OGR ES S
mic agents or insulin are usually reduced during ex-
ercise rehabilitation to prevent hypoglycemia, since
exercise increases sensitivity to insulin.96 An impor-
tant role of the cardiac-rehabilitation staff is to assist
primary care physicians with the monitoring of blood
pressure and diabetes. Patients are also taught tech-
niques of self-monitoring. Such surveillance may result
in adjustments of medications. In a study of cardiac re-
habilitation that involved 666 patients, surveillance led
to an alteration in the care received by 11 percent of
the patients, most of whom had uncontrolled blood
pressure, chest pain, or arrhythmia.97
Psychological Factors
From the patient’s point of view, the most prom-
inent effects of cardiac rehabilitation fall within the
psychological realm. Measures of anxiety, emotional
stress, lack of self-confidence, depression, social iso-
lation, and patient-reported quality of life all improve
after rehabilitation.23,33,45,98 Depression and social iso-
lation after a coronary event are associated with in-
creased mortality rates.46,99 Most cardiac-rehabilitation
programs include specific psychosocial interventions
such as stress management and psychiatric referrals
for patients with clinical depression. Patients enrolled
in programs that include psychosocial interventions
have greater reductions in anxiety and depression,
lower blood pressure, and lower rates of mortality and
recurrent cardiac events at two years than do those
enrolled in programs without a psychosocial compo-
nent.45
MODELS OF CARDIAC REHABILITATION
In the case-management model of cardiac rehabilita-
tion, patients undergo a comprehensive base-line eval-
uation of coronary risk factors and exercise capacity,
along with an assessment of physical and psycholog-
ical disability (Fig. 2). A case manager on the rehabil-
itation team (usually a nurse or exercise physiologist),
the medical director, or both review the assessment
of risks and outline a realistic, individualized exercise,
lifestyle, and pharmacologic program with short- and
long-term goals for reducing the risks (Table 2) (Fig.
2). The purpose of the base-line exercise stress test
is to determine whether the patient has exertional is-
chemia or arrhythmias, which might call for further
cardiac evaluation or treatment. The stress test also
serves as a basis for prescribing an exercise regimen
and determining when the patient can safely return
to work. Patients at low or moderate risk of an adverse
event, as determined by their performance on the
stress test, can often return to work within two weeks
after the test, once the work environment and job re-
quirements have been reviewed.100 Attention is then
focused on risk reduction.
A multifactorial risk-reduction model developed
by the Stanford Coronary Risk Intervention Project
showed that individualized changes in lifestyle and
N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org · 899
Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .
Copyright © 2001 Massachusetts Medical Society. All rights reserved.
medical treatment reduced the risks of disease pro-
gression and coronary events in patients with coro-
nary heart disease.13 The risk-reduction goals, which
were consistent with national guidelines,17,18 encom-
passed body weight, blood pressure, lipid levels, nu-
trition, and physical activity (Table 2). The program
was directed by a physician and coordinated by a nurse
case manager, with the assistance of dietitians and
psychologists. Short-term goals for modifying risk fac-
tors were based on the patient’s readiness for change
and resources, and were reevaluated periodically. Over
a four-year follow-up period, patients assigned to this
model of care, as compared with patients who re-
ceived usual care, had a 30 percent reduction in satu-
rated-fat intake, a 4 percent reduction in the body-
mass index, a 22 percent reduction in LDL cholesterol
levels, a 12 percent increase in HDL cholesterol levels,
and a 20 percent improvement in exercise capacity.
The rate of disease progression, assessed by angio-
graphic evaluation of coronary lesions, was reduced in
the intervention group, and the lesions were more like-
ly to regress in this group. The rates of major clinical
cardiac events and hospitalization were also significant-
ly decreased in the intervention group. Features of this
model of cardiac rehabilitation, such as the use of
nurse case managers, the establishment of goals for risk
reduction, and the medical management of lipid ab-
normalities, are being adapted to clinical practice.87,101
Patients considered to be at low or moderate risk
who do not have special needs can perform their pre-
scribed exercise at home.23,102 The optimal approach
combines a home-based walking program with inter-
mittent monitored exercise sessions at the cardiac-
rehabilitation center, exercise counseling, and period-
ic reassessment of risk factors. Older patients and those
with severe deconditioning who may need more com-
plex regimens of interval and resistance training benefit
from on-site supervision of exercise. As with weight-
loss programs, a detailed exercise diary of home-based
exercise increases compliance.74,92
COST EFFECTIVENESS OF
CARDIAC REHABILITATION
A comprehensive analysis of the costs of cardiac
rehabilitation after myocardial infarction or coronary
bypass surgery was performed in Sweden.103 At five
years, the rate of cardiac-related rehospitalization was
lower in the group of patients that had undergone
cardiac rehabilitation than in the control group, and
a larger proportion of patients in the rehabilitation
group had returned to work (53 percent vs. 38 per-
cent), with diminished costs for sick leave. In the over-
all analysis, the costs of rehabilitation were offset by
lower rates of hospitalization and increased work pro-
ductivity, resulting in a cost savings at five years of
$12,000 per patient for the Swedish health care sys-
tem. In the United States, medical care and unem-
ployment insurance are funded separately, and cost
 The Ne w E n g l a nd Jo ur n a l o f Me d ic i ne
effectiveness is usually expressed as dollars per year
of life saved. In a randomized, controlled trial by Old-
ridge et al., the cost effectiveness of cardiac rehabili-
tation, adjusted for the quality of life, was $9,200 per
year of life saved,104 whereas in a study that my col-
leagues and I performed, the cost effectiveness was
$4,950 per year of life saved.105 Both findings com-
pared favorably with the cost effectiveness of other
preventive measures in cardiology, with the exception
of smoking cessation.105
CHALLENGES AND CONCLUSIONS
Cardiac rehabilitation has primarily, but not exclu-
sively, been used and studied in patients at relatively
high socioeconomic levels. However, the prevalence
of coronary heart disease among persons at lower
socioeconomic levels is increasing.106 A challenge to
clinicians who provide cardiac rehabilitation will be to
extend its benefits to indigent107 and minority108 pop-
ulations, as well as to the populations of developing
countries where rates of coronary heart disease are
increasing.
Only 10 percent to 47 percent of eligible patients
currently participate in formal programs of cardiac
rehabilitation.14,19,109 All patients hospitalized with a
diagnosis of coronary heart disease should be system-
atically evaluated by a specialist in preventive cardi-
ology and cardiac rehabilitation. An individualized
program should be developed in close collaboration
with the patient’s primary care physician. This ap-
proach minimizes the likelihood of subsequent coro-
nary events and maximizes functional capacity. The in-
tensity of the program would depend on the patient’s
readiness for behavioral change and on the clinical
and demographic characteristics of the patient.
Whereas for many patients, particularly those who
are elderly, such a program will consist of supervised
exercise and counseling at a cardiac-rehabilitation cen-
ter, for some — particularly younger patients — the
program will focus on the modification of risk factors,
combined with a home-based exercise program. The
base-line assessment of risk factors and exercise capac-
ity should be a checkpoint for decisions about the use
of preventive medications, such as aspirin, beta-adre-
nergic blockers, angiotensin-converting–enzyme in-
hibitors, and lipid-lowering medications.18 The exercise
program must be individualized, whether the focus is
on physical functioning, modification of risk factors,
weight loss, or general prevention. Finally, the cardiac-
rehabilitation team needs to specify the goals of reha-
bilitation as measurable physical, behavioral, and risk-
factor outcomes linked to clinical outcomes. If this is
done effectively, the combination of rehabilitation and
secondary prevention will become the standard of care
for patients with coronary heart disease.
Supported in part by grants from the National Institutes of Health (RO1
AG15114-03) and the General Clinical Research Center of the University
of Vermont (RR-109).
900 · N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org
Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .
Copyright © 2001 Massachusetts Medical Society. All rights reserved.
I am indebted to Benjamin Littenberg, M.D., Eric T. Poehlman,
Ph.D., and Kathy Berra, M.S.N., for their review of the manuscript
and helpful comments.
REFERENCES
1. Heart and stroke facts: 1999 statistical supplement. Dallas: American
Heart Association, 1999.
2. Pinsky JL, Jette AM, Branch LG, Kannel WB, Feinleib M. The Fra-
mingham Disability Study: relationship of various coronary heart disease
manifestations to disability in older persons living in the community. Am
J Public Health 1990;80:1363-7.
3. LaPlante MP. Data on disability from the National Health Interview
Survey, 1983-1985. Washington, D.C.: National Institute on Disability and
Rehabilitation Research, 1989.
4. Wenger N, Hellerstein HK, Blackburn H, Castranova SJ. Uncomplicat-
ed myocardial infarction: current physician practice in patient management.
JAMA 1973;224:511-4.
5. Hellerstein HK. Exercise therapy in coronary disease. Bull N Y Acad
Med 1968;44:1028-47.
6. Kavanagh T, Shephard RJ, Doney H, Pandit V. Intensive exercise in cor-
onary rehabilitation. Med Sci Sports 1973;5:34-9.
7. Pashkow FJ. Issues in contemporary cardiac rehabilitation: a historical
perspective. J Am Coll Cardiol 1993;21:822-34.
8. Newby LK, Eisenstein EL, Califf RM, et al. Cost effectiveness of early
discharge after uncomplicated acute myocardial infarction. N Engl J Med
2000;342:749-55.
9. Oldridge NB, Guyatt GH, Fischer ME, Rimm AA. Cardiac rehabilita-
tion after myocardial infarction: combined experience of randomized clin-
ical trials. JAMA 1988;260:945-50.
10. O’Connor GT, Buring JE, Yusuf S, et al. An overview of randomized
trials of rehabilitation with exercise after myocardial infarction. Circulation
1989;80:234-44.
11. Ornish D, Scherwitz LW, Billings JH, et al. Intensive lifestyle changes
for reversal of coronary heart disease. JAMA 1998;280:2001-7. [Erratum,
JAMA 1999;281:1380.]
12. Schuler G, Hambrecht R , Schlierf G, et al. Regular physical exercise
and low-fat diet: effects on progression of coronary artery disease. Circu-
lation 1992;86:1-11.
13. Haskell WL, Alderman EL, Fair JM, et al. Effects of intensive multiple
risk factor reduction on coronary atherosclerosis and clinical cardiac events
in men and women with coronary artery disease: the Stanford Coronary
Risk Intervention Project (SCRIP). Circulation 1994;89:975-90.
14. Wenger NK, Froehlicher ES, Smith LK, et al. Cardiac rehabilitation:
clinical practice guidelines. Rockville, Md.: Agency for Health Care Policy
and Research and the National Heart, Lung, and Blood Institute, 1995.
(AHCPR publication no. 96-0672.)
15. Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse
coronary heart disease? The Lifestyle Heart Trial. Lancet 1990;336:129-33.
16. Niebauer J, Hambrecht R , Velich T, et al. Attenuated progression of
coronary artery disease after 6 years of multifactorial risk intervention: role
of physical exercise. Circulation 1997;96:2534-41.
17. Balady G, Ades PA, Comoss P, et al. Core components of cardiac re-
habilitation/secondary prevention programs: a statement for healthcare
professionals from the American Heart Association and the American As-
sociation of Cardiovascular and Pulmonary Rehabilitation Writing Group.
Circulation 2000;102:1069-73.
18. Smith SC Jr, Blair SN, Criqui MH, et al. Preventing heart attack and
death in patients with coronary disease. Circulation 1995;92:2-4.
19. Thomas RJ, Miller NH, Lamendola C, et al. National Survey on Gen-
der Differences in Cardiac Rehabilitation Programs: patient characteristics
and enrollment patterns. J Cardiopulm Rehabil 1996;16:402-12.
20. Ades PA, Waldmann ML, McCann WJ, Weaver SO. Predictors of car-
diac rehabilitation participation in older coronary patients. Arch Intern
Med 1992;152:1033-5.
21. Ades PA, Waldmann ML, Polk DM, Coflesky JT. Referral patterns and
exercise response in the rehabilitation of female coronary patients aged
»62 years. Am J Cardiol 1992;69:1422-5.
22. DeBusk RF, Miller NH, Superko HR , et al. A case-management sys-
tem for coronary risk factor modification after acute myocardial infarction.
Ann Intern Med 1994;120:721-9.
23. Ades PA, Pashkow FJ, Fletcher G, Pina IL, Zohman LR, Nestor JR.
A controlled trial of cardiac rehabilitation in the home setting using elec-
trocardiographic and voice transtelephonic monitoring. Am Heart J 2000;
139:543-8.
24. Hambrecht R , Wolf A, Gielen S, et al. Effect of exercise on coronary
endothelial function in patients with coronary artery disease. N Engl J Med
2000;342:454-60.
25. Kaufmann P, Mandinov L, Hess OM. Coronary stenosis vasoconstric-
tion: impact on myocardial ischaemia. Eur Heart J 1997;18:1853-9.
 MED IC A L PR OGR ES S
26. Ruzumna P, Gheorghiade M, Bonow RO. Mechanisms and manage-
ment of heart failure due to diastolic dysfunction. Curr Opin Cardiol 1996;
11:269-75.
27. Neill WA, Branch LG, DeJong G, et al. Cardiac disability: the impact
of coronary heart disease on patients’ daily activities. Arch Intern Med
1985;145:1642-7.
28. Chirikos TN, Nickel JT. Socioeconomic determinants of continuing
functional disablement from chronic disease episodes. Soc Sci Med 1986;
22:1329-35.
29. Ades PA. Cardiac rehabilitation in older coronary patients. J Am Geri-
atr Soc 1999;47:98-105.
30. Ades PA, Grunvald MH. Cardiopulmonary exercise testing before and
after conditioning in older coronary patients. Am Heart J 1990;120:585-9.
31. Van Camp SP, Peterson RA. Cardiovascular complications of outpa-
tient cardiac rehabilitation programs. JAMA 1986;256:1160-3.
32. Franklin BA, Bonzheim K, Gordon S, Timmis GC. Safety of medically
supervised outpatient cardiac rehabilitation exercise therapy: a 16-year fol-
low-up. Chest 1998;114:902-6.
33. Ades PA, Maloney A, Savage P, Carhart RL Jr. Determinants of phys-
ical functioning in coronary patients: response to cardiac rehabilitation.
Arch Intern Med 1999;159:2357-60.
34. Redwood DR, Rosing DR, Epstein SE. Circulatory and symptomatic
effects of physical training in patients with coronary-artery disease and an-
gina pectoris. N Engl J Med 1972;286:959-65.
35. Ades PA, Grunvald MH, Weiss RM, Hanson JS. Usefulness of myo-
cardial ischemia as predictor of training effect in cardiac rehabilitation after
acute myocardial infarction or coronary artery bypass grafting. Am J Car-
diol 1989;63:1032-6.
36. Ehsani AA, Biello DR , Schultz J, Sobel BE, Holloszy JO. Improve-
ment of left ventricular contractile function by exercise training in patients
with coronary artery disease. Circulation 1986;74:350-8. [Erratum, Circu-
lation 1986;74:938.]
37. Ades PA, Waldmann ML, Meyer WL, et al. Skeletal muscle and car-
diovascular adaptations to exercise conditioning in older coronary patients.
Circulation 1996;94:323-30.
38. Hagberg JM. Physiologic adaptations to prolonged high-intensity ex-
ercise training in patients with coronary artery disease. Med Sci Sports
Exerc 1991;23:661-7.
39. Warner JG Jr, Brubaker PH, Zhu Y, et al. Long-term (5-year) changes
in HDL cholesterol in cardiac rehabilitation patients. Do sex differences ex-
ist? Circulation 1995;92:773-7.
40. Brochu M, Poehlman ET, Savage P, Fragnoli-Munn K, Ross S, Ades
PA. Modest effects of exercise training alone on coronary risk factors and
body composition in coronary patients. J Cardiopulm Rehabil 2000;20:
180-8.
41. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coro-
nary vasodilator dysfunction on adverse long-term outcome of coronary
heart disease. Circulation 2000;101:1899-906.
42. Malfattoo G, Facchini M, Sala L, Branzi G, Bragato R, Leonetti G.
Effects of cardiac rehabilitation and beta-blocker therapy on heart rate vari-
ability after first acute myocardial infarction. Am J Cardiol 1998;81:834-
40.
43. Stratton J, Chandler WL, Schwartz RS, et al. Effects of physical con-
ditioning on fibrinolytic variables and fibrinogen in young and old healthy
adults. Circulation 1991;83:1692-7.
44. Suzuki T, Yamauchi K, Yamada Y, et al. Blood coagulability and fibri-
nolytic activity before and after physical training during the recovery phase
of acute myocardial infarction. Clin Cardiol 1992;15:358-64.
45. Linden W, Stossel C, Maurice J. Psychosocial interventions for patients
with coronary artery disease: a meta-analysis. Arch Intern Med 1996;156:
745-52. [Erratum, Arch Intern Med 1996;156:2302.]
46. Frasure-Smith N, Lesperance F, Gravel G, et al. Social support, depres-
sion, and mortality during the first year after myocardial infarction. Circu-
lation 2000;101:1919-24.
47. Wannamethee SG, Shaper AG, Walker M. Physical activity and mortal-
ity in older men with diagnosed coronary heart disease. Circulation 2000;
102:1358-63.
48. Konstam M, Dracup K, Baker D, et al. Heart failure: evaluation and
care of patients with left-ventricular systolic dysfunction: clinical practice
guideline. No. 11. Rockville, Md.: Agency for Health Care Policy and Re-
search, 1994. (AHCPR publication no. 94-0612.)
49. Keteyian SJ, Levine AB, Brawner CA, et al. Exercise training in pa-
tients with heart failure: a randomized, controlled trial. Ann Intern Med
1996;124:1051-7.
50. Coats AJ, Adamopoulos S, Radaelli A, et al. Controlled trial of phys-
ical training in chronic heart failure: exercise performance, hemodynamics,
ventilation, and autonomic function. Circulation 1992;85:2119-31.
51. Hambrecht R, Niebauer J, Fiehn E, et al. Physical training in patients
with stable chronic heart failure: effects on cardiorespiratory fitness and ul-
N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org · 901
Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .
Copyright © 2001 Massachusetts Medical Society. All rights reserved.
trastructural abnormalities of leg muscles. J Am Coll Cardiol 1995;25:
1239-49.
52. Belardinelli R , Georgiou D, Cianci G, Purcaro A. Randomized, con-
trolled trial of long-term moderate exercise training in chronic heart fail-
ure: effects on functional capacity, quality of life, and clinical outcome. Cir-
culation 1999;99:1173-82.
53. Stevenson LW, Steimle AE, Fonarow G, et al. Improvement in exercise
capacity of candidates awaiting heart transplantation. J Am Coll Cardiol
1995;25:163-70.
54. Kobashigawa JA, Leaf DA, Lee N, et al. A controlled trial of exercise
rehabilitation after heart transplantation. N Engl J Med 1999;340:272-7.
[Erratum, N Engl J Med 1999;340:976.]
55. Mendoza SG, Carrasco H, Zerpa A, et al. Effect of physical training
on lipids, lipoproteins, apolipoproteins, lipases, and endogenous sex hor-
mones in men with premature myocardial infarction. Metabolism 1991;40:
368-77.
56. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary
prevention of coronary heart disease in men with low levels of high-density
lipoprotein cholesterol. N Engl J Med 1999;341:410-8.
57. Lavie CJ, Milani RV. Effects of cardiac rehabilitation and exercise train-
ing in obese patients with coronary artery disease. Chest 1996;109:52-6.
58. Dylewicz P, Bienkowska S, Szczesniak L, et al. Beneficial effect of
short-term endurance training on glucose metabolism during rehabilitation
after coronary bypass surgery. Chest 2000;117:47-51.
59. Schairer JR , Kostelnik T, Proffitt SM, et al. Caloric expenditure during
cardiac rehabilitation. J Cardiopulm Rehab 1998;18:290-4.
60. Savage PD, Brochu M, Scott P, Ades PA. Low caloric expenditure in
cardiac rehabilitation. Am Heart J 2000;140:527-33.
61. Brochu M, Poehlman ET, Ades PA. Obesity, body fat distribution, and
coronary artery disease. J Cardiopulm Rehabil 2000;20:96-108.
62. Mertens DJ, Kavanagh T, Campbell RB, Shephard RJ. Exercise with-
out dietary restriction as a means to long-term fat loss in the obese cardiac
patient. J Sports Med Phys Fitness 1998;38:310-6.
63. Ades PA, Ballor DL, Ashikaga T, Utton JL, Nair KS. Weight training
improves walking endurance in healthy elderly persons. Ann Intern Med
1996;124:568-72.
64. Williams MA, Maresh CM, Esterbrooks DJ, Harbrecht JJ, Sketch
MH. Early exercise training in patients older than age 65 years compared
with that in younger patients after acute myocardial infarction or coronary
artery bypass grafting. Am J Cardiol 1985;55:263-6.
65. Lavie CJ, Milani RV, Littman AB. Benefits of cardiac rehabilitation and
exercise training in secondary coronary prevention in the elderly. J Am Coll
Cardiol 1993;22:678-83.
66. Ades PA, Waldmann ML, Gillespie C. A controlled trial of exercise
training in older coronary patients. J Gerontol A Biol Sci Med Sci 1995;
50:M7-M11.
67. Fragnoli-Munn K, Savage PD, Ades PA. Combined resistive-aerobic
training in older patients with coronary artery disease early after myocardial
infarction. J Cardiopulm Rehabil 1998;18:416-20.
68. Oldridge NB. Compliance and dropout in cardiac exercise rehabilita-
tion. J Cardiac Rehabil 1984;4:166-77.
69. Burke LE, Dunbar-Jacob JM, Hill MN. Compliance with cardiovascu-
lar disease prevention strategies: a review of the research. Ann Behav Med
1997;19:239-63.
70. Dunbar-Jacob J, Dwyer K, Dunning EJ. Compliance with antihyper-
tensive regimen: a review of the research in the 1980s. Ann Behav Med
1991;13:31-9.
71. Kruse WH-H. Compliance with treatment of hyperlipoproteinemia in
medical practice and clinical trials. In: Kramer JA, Spilker B, eds. Patient
compliance in medical practice and clinical trials. New York: Raven Press,
1991:175-86.
72. Carlson JJ, Johnson JA, Franklin BA, VanderLaan RL. Program par-
ticipation, exercise adherence, cardiovascular outcomes, and program cost
of traditional versus modified cardiac rehabilitation. Am J Cardiol 2000;86:
17-23.
73. Lee JY, Jensen BE, Oberman A, Fletcher GF, Fletcher BJ, Raczynski
JM. Adherence in the training levels comparison trial. Med Sci Sports
Exerc 1996;28:47-52.
74. Oldridge NB, Jones NL. Improving patient compliance in cardiac ex-
ercise rehabilitation: effects of written agreement and self-monitoring.
J Cardiac Rehabil 1983;3:257-62.
75. Rossouw JE, Lewis B, Rifkind BM. The value of lowering cholesterol
after myocardial infarction. N Engl J Med 1990;323:1112-9.
76. Taylor CB, Houston-Miller N, Killen JD, DeBusk RF. Smoking cessa-
tion after acute myocardial infarction: effects of a nurse-managed interven-
tion. Ann Intern Med 1990;113:118-23.
77. Wilhelmsson C, Vedin JA, Elmfeldt D, Tibblin G, Wilhelmsen L.
Smoking and myocardial infarction. Lancet 1975;1:415-20.
78. Wilson K, Gibson N, Willan A, Cook D. Effect of smoking cessation
 The Ne w E n g l a nd Jo ur n a l o f Me d ic i ne
on mortality after myocardial infarction: meta-analysis of cohort studies.
Arch Intern Med 2000;160:939-44.
79. Scandinavian Simvastatin Survival Study Group. Randomised trial of
cholesterol lowering in 4444 patients with coronary heart disease. Lancet
1994;344:1383-9.
80. Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP,
Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin thera-
py on coronary atherosclerosis and coronary venous bypass grafts. JAMA
1987;257:3233-40. [Erratum, JAMA 1988;259:2698.]
81. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on
coronary events after myocardial infarction in patients with average choles-
terol levels. N Engl J Med 1996;335:1001-9.
82. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery
disease as a result of intensive lipid-lowering therapy in men with high lev-
els of apolipoprotein B. N Engl J Med 1990;323:1289-98.
83. Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults. Executive summary of the Third Report of the Na-
tional Cholesterol Education Program (NCEP) Expert Panel on Detec-
tion, Evaluation, and Treatment of High Blood Cholesterol in Adults
(Adult Treatment Panel III). JAMA 2001;285:2486-97.
84. Sueta C, Chowdhury M, Boccuzzi SJ. Analysis of the degree of under-
treatment of hyperlipidemia and congestive heart failure secondary to cor-
onary artery disease. Am J Cardiol 1999;83:1303-7. [Erratum, Am J Car-
diol 1999;84:1143.]
85. McBride P, Schrott HG, Plane MB, Underbakke G, Brown RL. Pri-
mary care practice adherence to National Cholesterol Education Program
guidelines for patients with coronary heart disease. Arch Intern Med 1998;
158:1238-44.
86. Bramlet DA, King H, Young L, Witt JR, Stoukides CA, Kaul AF.
Management of hypercholesterolemia: practice patterns for primary care
providers and cardiologists. Am J Cardiol 1997;80:39H-44H.
87. Ades PA, Savage PD, Poehlman ET, Brochu M, Fragnoli-Munn K,
Carhart RL Jr. Lipid lowering in the cardiac rehabilitation setting. J Car-
diopulm Rehabil 1999;19:255-60.
88. Singh RB, Rastogi SS, Verma R, et al. Randomized controlled trial of
cardioprotective diet in patients with recent acute myocardial infarction:
results of one year of follow up. BMJ 1992;304:1015-9.
89. Katzel LI, Coon PJ, Dengel J, Goldberg AP. Effects of an American
Heart Association Step I diet and weight loss on lipoprotein lipid levels in
obese men with silent myocardial ischemia and reduced high-density lipo-
protein cholesterol. Metabolism 1995;44:307-14.
90. Calles-Escandon J, Ballor D, Harvey-Berino J, Ades P, Tracy R, Sobel
B. Amelioration of the inhibition of fibrinolysis in elderly, obese subjects
by moderate energy intake restriction. Am J Clin Nutr 1996;64:7-11.
91. Harvey-Berino J. Weight loss in the clinical setting: applications for
cardiac rehabilitation. Coron Artery Dis 1998;9:795-8.
92. Foreyt JP, Goodrick GK. Evidence for success of behavior modifica-
tion in weight loss and control. Ann Intern Med 1993;119:698-701.
93. Tremblay A, Doucet E, Imbeault P, Mauriege P, Despres JP, Richard
902 · N Engl J Med, Vol. 345, No. 12 · September 20, 2001 · www.nejm.org
Downloaded from www.nejm.org at UNIVERSITY OF LJUBLJANI on February 21, 2008 .
Copyright © 2001 Massachusetts Medical Society. All rights reserved.
D. Metabolic fitness in active reduced-obese individuals. Obes Res 1999;7:
556-63.
94. Kokkinos PF, Papademetriou V. Exercise and hypertension. Coron Ar-
tery Dis 2000;11:99-102.
95. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects
of dietary patterns on blood pressure. N Engl J Med 1997;336:1117-24.
96. Ruderman N, Devlin J. The health professional’s guide to diabetes and
exercise. Alexandria, Va.: American Diabetes Association, 1995.
97. Vongvanich P, Bairey Merz CN. Supervised exercise and electrocardio-
graphic monitoring during cardiac rehabilitation: impact on patient care.
J Cardiopulm Rehabil 1996;16:233-8.
98. Oldridge N, Guyatt G, Jones N, et al. Effects on quality of life with
comprehensive rehabilitation after acute myocardial infarction. Am J Car-
diol 1991;67:1084-9.
99. Rosenman RH, Brand RJ, Jenkins D, Friedman M, Straus R, Wurm
M. Coronary heart disease in Western Collaborative Group Study: final fol-
low-up experience of 8 1/2 years. JAMA 1975;233:872-7.
100. Dennis C, Houston-Miller N, Schwartz RG, et al. Early return to
work after uncomplicated myocardial infarction: results of a randomized
trial. JAMA 1988;260:214-20.
101. Gordon NF, Haskell WL. Comprehensive cardiovascular disease risk
reduction in a cardiac rehabilitation setting. Am J Cardiol 1997;80:69H-
73H.
102. Miller NH, Haskell WL, Berra K, DeBusk RF. Home versus group
exercise training for increasing functional capacity after myocardial infarc-
tion. Circulation 1984;70:645-9.
103. Levin LA, Perk J, Hedback B. Cardiac rehabilitation: a cost analysis.
J Intern Med 1991;230:427-34.
104. Oldridge N, Furlong W, Feeny D, et al. Economic evaluation of car-
diac rehabilitation soon after acute myocardial infarction. Am J Cardiol
1993;72:154-61.
105. Ades PA, Pashkow FJ, Nestor JR. Cost-effectiveness of cardiac reha-
bilitation after myocardial infarction. J Cardiopulm Rehabil 1997;17:222-
31.
106. Salomaa V, Niemela M, Miettinen H, et al. Relationship of socioeco-
nomic status to the incidence and prehospital, 28-day, and 1-year mortality
rates of acute coronary events in the FINMONICA myocardial infarction
register study. Circulation 2000;101:1913-8.
107. Friedman DB, Williams AN, Levine BD. Compliance and efficacy of
cardiac rehabilitation and risk factor modification in the medically indigent.
Am J Cardiol 1997;79:281-5.
108. Cannistra LB, O’Malley CJ, Balady GJ. Comparison of outcome of
cardiac rehabilitation in black women and white women. Am J Cardiol
1995;75:890-3.
109. Evenson KR , Rosamond WD, Luepker RV. Predictors of outpatient
cardiac rehabilitation utilization: the Minnesota Heart Surgery Registry.
J Cardiopulm Rehabil 1998;18:192-8.
Copyright © 2001 Massachusetts Medical Society.