Cardiol Clin 21 (2003) 435–448

Effects of exercise and cardiac rehabilitationon cardiovascular outcomes

Philip A. Ades, MDa,*, Nieta M. Green, MDb, Cesar E. Coello, MDc

aDivision of Cardiology, Department of Medicine, University of Vermont College of Medicine,

Fletcher-Allen Health Care, Burlington, VT 05401, USAbDepartment of Medicine, University of Vermont College of Medicine,

Fletcher-Allen Health Care, Burlington, VT 05401, USAc305 West Jackson Street, Suite LL01, Carbondale, IL 62901, USA

The 1995 clinical practice guidelines for cardiacrehabilitation [1] state that ‘‘Cardiac rehabilita-tion services are comprehensive, long-term pro-

grams involving medical evaluation, prescribedexercise, cardiac risk-factor modification, educa-tion and counseling. These programs are designed

to limit the physiologic and psychologic effects ofcardiac illness, reduce the risk for sudden death orreinfarction, control cardiac symptoms, stabilize

or reverse the atherosclerotic process, and en-hance the psychosocial and vocational status ofpatients with coronary heart disease.’’

Cardiac rehabilitation was originally conceivedto counteract the deconditioning and comorbid-ities associated with prolonged bed rest after amyocardial infarction [2]. Highly supervised and

carefully monitored outpatient cardiac rehabilita-tion programs were established and were limitedto low-risk patients with coronary heart disease

(CHD) [2]. As the hospital stay for a myocardialinfarction has become shorter, deconditioning andrelated disability are minimized [3]. Contempo-

rary cardiac rehabilitation has taken a morecomprehensive approach, with a broader rangeof participating patients, including patients whohave had coronary bypass surgery or percutane-

ous coronary interventions and those who have

A version of this article originally appeared in the

January 2000 issue of Medical Clinics of North America.

* Corresponding author.

E-mail address: Philip.Ades@vtmednet.org

(P.A. Ades).

0733-8651/03/$ - see front matter � 2003 Elsevier Inc. All rig

doi:10.1016/S0733-8651(03)00056-0

chronic heart failure [1]. The prevention of secondcoronary events stands alongside the maintenanceof physical function capacity as a major goal [4].

Cardiac rehabilitation services commence witha comprehensive intake evaluation of the patientincluding a clinical status review, a baseline stress

test, and documentation of body weight, lipids,glucose, nutritional status, and baseline physicalactivity [5]. A supervised exercise-training pro-

gram with both aerobic and resistance trainingcomponents is designed. Cardiac risk factors areassessed, and a lifestyle-based or pharmaceutic

treatment plan is set up with short-term and long-term treatment goals based on broadly acceptedalgorithms [5,6]. The need for stress managementprograms and individualized or group nutritional

counseling is assessed. Goals of a personalizednutritional program include the application ofa diet appropriate for the treatment of obesity,

hypertension, hyperlipidemia, insulin resistance,and diabetes.

The effects of comprehensive cardiac rehabil-

itation are shown in Box 1.Relevant cardiovascular outcomes of cardiac

rehabilitation can be classified as:

1. Primary clinical outcomes2. Intermediate clinical outcomes

3. Quality-of-life outcomes

Primary clinical outcomes are those that can be

directly appreciated by the patient, such as thepresence of symptoms, functional capacity, andthe occurrence of cardiac events. Intermediate

hts reserved.

436 P.A. Ades et al / Cardiol Clin 21 (2003) 435–448

Box 1. Effects of comprehensive cardiac rehabilitation

CardiovascularDecreases myocardial oxygen demandIncreases stroke volumeDecreases heart rate blood pressure product at submaximal workloadIncreases anginal thresholdIncreases vagal tone, decreased catecholamine levelsImproves coronary endothelial vasodilatory capacityOptimizes antihypertensive therapy

Skeletal muscleIncreases muscle fiber areaIncreases capillary densityIncreases skeletal muscle vasodilatory capacityIncreases oxidative capacity

MetabolicImproves lipid profile and permits monitoring of lipid-lowering therapyImproves carbohydrate metabolismFavorably modifies body composition and body weight

PsychologicLowers measures of emotional stress, anxiety, and somatization scoresImproves measures of quality of lifeHastens improvement of depressive symptoms

From Ades PA, Coello CE. Effects of exercise and cardial rehabilitation on cardiovascular outcomes.Med Clin N Am 2000; 84(1):251–65.

outcomes include factors that require measure-ment, such as lipid levels, glucose levels, and

blood pressure. These outcomes can modify theclinical and atherosclerotic process but are notclinical or symptomatic end points (Table 1).

Finally, quality-of-life outcomes reflect the pa-tient’s perception of his or her health status.Certain quality-of-life issues such as socialisolation and depression have been linked to

altered prognosis in patients with coronary heartdisease [7,8]. Other quality-of-life measures suchas physical functioning directly relate to the

patient’s ability to live independently in the homesetting. The effects of exercise training alone and,more importantly, the value of comprehensive

cardiac rehabilitation are reviewed from the pointof view of individual cardiovascular outcomes.

Exercise training and primary clinical outcomes

The success of a therapeutic intervention in the

presence of coronary artery disease can bemeasured directly by its effect on prolongation oflife (mortality), on the prevention of recurrent

coronary events, hospitalizations, and symptoms(morbidity), on functional capacity (exercise tol-

erance), and on patient-perceived quality of life.These outcomes are primary clinical outcomes thatcan be directly appreciated by the patient.

Cardiovascular mortality

The impact of exercise training on cardiovas-cular mortality in CHD patients has been wellstudied. Several individual, randomized, con-

trolled trials indicate a mortality benefit [9–11];however, meta-analytic techniques have provideda particularly useful tool to study the effect on

overall mortality of cardiac rehabilitation aftermyocardial infarction. The studies of Oldridgeand O’Connor [12,13] reported a 25% reduction

in 3-year mortality in patients who participate incardiac rehabilitation after having experienceda myocardial infarction, compared with controlgroups. In this meta-analysis, more than 4000

patients from 21 randomized, controlled trialswere combined. Most patients in these studieswere men and were younger than 65 years of age.

Most of these studies took place before the

437P.A. Ades et al / Cardiol Clin 21 (2003) 435–448

Table 1

Effect of exercise training and nutritional modification on serum lipid values and body weight in coronary patients

Study Population Intervention

%

Change

LDL-C

levels

%

Change

HDL-C

levels

%

Change

triglyc

levels

%

Change

in body

weight

Schuler 1992

Germany

113 male patients with

stable angina.

Angiography-

confirmed CAD

Home exercise,

AHA phase

III diet for 1 year.

No lipid-lowering drugs

�11% +3% �24% �5%

Haskell SCRIP

1994 USA

300 (13% women).

Angiography-

confirmed CAD

Moderate intensity

exercise, diet, lipid-

lowering drugs

for 4 years

�22% +12% +20% �4%

Ornish Lifestyle

Heart Trial

1990 USA

48 (12% women).

Angiography-

confirmed CAD

10% fat vegetarian diet,

moderate exercise,

stress management

for 1 year.

No lipid-

lowering drugs.

�38% �9% +13% �11%

Abbreviations: AHA, American Heart Associations; CAD, coronary artery disease; HDL-C, high density lipoprotein

cholesterol; LDL-C, low density lipoprotein cholesterol; Triglyc, triglyceride.

From Ades PA, Coello CE. Effects of exercise and cardiac rehabilitation on cardiovascular outcomes. Med Clin N

Am 2000;84(1):251–65.

widespread use of thrombolytic agents, b-adren-ergic blocking agents, angiotensin-convertingenzyme (ACE) inhibitors, and acute percutaneous

coronary revascularization procedures which havealso resulted in an overall decrease in postmyo-cardial infarction mortality rates [14].

More recently, the Cochrane Database [15]also performed a systematic meta-analysis toevaluate the efficacy of exercise alone and exerciseas a component of comprehensive cardiac re-

habilitation in men and women with documentedcoronary artery disease. It was found that bothexercise alone and exercise as a component of

multifactorial rehabilitation were associated withdecreases in overall mortality (by 27% and 13%,respectively) compared with control groups. The

database oddly demonstrated that exercise aloneis more efficacious than comprehensive care. Theauthors, however, acknowledge some weaknesses

in the reviewed trials, including insufficient powerof individual trials, poor methods of randomiza-tion, and a lack of data relating to the use ofcardiac medication.

In patients with chronic heart failure charac-terized by the presence of primarily systolic leftventricular dysfunction and New York Heart

Association class II and III symptoms, a random-ized, controlled trial of exercise training docu-mented a significant decrease in overall mortality,

an increase in exercise capacity and quality of life,

and a decreased rate of cardiac hospitalizations(Fig. 1) [16]. Other studies in this high-riskpopulation documented that exercise seems to be

safe and that exercise training is associated withan improved exercise tolerance and improvedquality of life, although the total number of pa-

tients studied has been relatively limited [17–19].Supervised exercise training in the cardiac

rehabilitation setting has been documented to beextremely safe. A multicenter report of 30 pro-

grams estimates a mortality rate of 1 death per116,000 patient-hours [20]. Another more recentand larger study that included data from 142

programs in the United States documented amortality rate of 1 per 784,000 patient-hours [21].Thus, it is clear that the beneficial effects of car-

diac rehabilitation can be attained without sub-stantial exercise-related cardiovascular mortality.

Cardiovascular morbidity

The most frequently reported morbidity out-come following cardiac rehabilitation is the occur-

rence of nonfatal myocardial infarctions or cardiachospitalizations for acute coronary syndromes[22–25]. In view of the demonstrated decrease in

overall cardiovascular mortality, a reduction in re-current cardiac events including nonfatal myocar-dial infarctions is to be expected. Reports rangingfrom the 1970s to the 2000s have not consistently

438 P.A. Ades et al / Cardiol Clin 21 (2003) 435–448

Fig. 1. Effects of exercise training on cardiovascular outcomes in patients with chronic heart failure. *, P<0.05 versus

controls; All events, cardiovascular death, myocardial infarction, cardiac rehospitalization; lighter bars, training group;

darker bars, control group. (Adapted from Belardinelli R, Georgiou D, Cianci G, et al. Randomized, controlled trial of

long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical

outcome. Circulation 1999;99:1173–82; with permission.)

shown a decrease in the recurrence of nonfatal

myocardial infarctions after exercise alone[12,13,15]. A controlled trial of cardiac rehabilita-tion from Sweden, however, did demonstrate

a significant decrease in recurrence of nonfatalmyocardial infarctions after cardiac rehabilitation(28.6% versus 39.9%) over 5 years [11]. Thisdecreased morbidity was also associated with

a lesser need for antianginal medication at 1 and5 years, fewer rehospitalizations for cardiac prob-lems, and fewer visits to the emergency department

[11]. Furthermore, the multifactorial diet andexercise trials of Haskell [26] and Ornish [27] wereassociated with decreased cardiac hospitalizations.

Stable exertional angina is the cardinal symp-tom reported by patients presenting with coronaryartery disease who are subsequently candidates forcardiac rehabilitation programs. Most studies

examining the effect of exercise training on patientswith chronic stable angina have reported signifi-cant improvements in anginal severity compared

with randomized controls [28]. In general the angi-nal threshold is increased after training, and insome patients angina no longer occurs [11,27–30].

Exercise tolerance

Cardiac rehabilitation exercise training consis-tently results in significant improvements in peakexercise capacity in patients with known coronary

artery disease [1]. Early studies primarily included

younger male patients; however, more recentreports documented similar benefits in womenand elderly patients [31–34].

The beneficial effects of exercise training aremost evident when an adequate threshold ofintensity and duration of training are used. Intrials in which patients exercise more than 8 weeks

at 60% or more of the maximal heart rate reachedat the baseline test, exercise tolerance on thetreadmill increased by 30% to 50%, and peak

oxygen consumption increased by 15% to 20%[1]. Randomized, controlled trials comparing theeffects of higher-intensity training document

greater improvement in exercise tolerance in theshort term, but long-term benefits were less clearwhen assessed after 1 year [35,36].

The magnitude of the exercise tolerance

improvement seems to be more noticeable inindividuals who are less fit at baseline [37]. Someauthors suggest that older patients may require

more prolonged training than younger patients toachieve the same relative improvements in exercisetolerance [38], although this finding is not

universal [39]. Exercise training has significantpositive effects on exercise tolerance and selectedrisk factors, even in patients with well-preserved

exercise capacity at baseline [40].Patients with stable chronic heart failure

secondary to ischemic cardiomyopathy or dilated

439P.A. Ades et al / Cardiol Clin 21 (2003) 435–448

cardiomyopathy benefit symptomatically fromphysical training programs with an increase inexercise tolerance. An improvement in clinicalstatus is achieved with moderate doses of physical

activity (60% of peak aerobic capacity) and isnoted even in more severe stages of heart failure[16]. There is evidence that the favorable effects of

exercise training in patients with ischemic cardio-myopathy result from both peripheral adapta-tions, such as increased oxidative enzyme capacity

and capillarity [41], and from improved coronaryperfusion as demonstrated by increased thalliumuptake during exercise [16].

Strength

Resistance (weight-based) training optimizesstrength, endurance, and physical function inolder patients with CHD [42,43]. A lack of muscle

strength has been correlated with low physicalfunction [44]. In a randomized, controlled studycomparing 6 months of resistance training with

flexibility training in older women with CHD, theresistance-training group demonstrated significantobjective improvement in strength, endurance,balance, and coordination [42]. Ironically, when

questioned, these patients did not subjectivelydescribe increased activity. Increased strengthdoes not spontaneously result in an increased

activity profile in the home setting. Patients oftenlimit physical activity because of a fear of adverseconsequences rather than because of true cardio-

vascular symptoms. Formal activity counselingcoordinated with cardiac rehabilitation can dispelthe patient’s incorrect notions about the safety of

strength-related activities, thus maximizing thebeneficial effects of resistance training [42].

Pollock et al [45] described the effectivenessof resistance training in low- to moderate-risk

patients and the additive benefits of combining re-sistance training with aerobic exercise. Together,the two exercise modalities can have a beneficial

effect on physical functioning, strength, and gait,along with objective benefits in glucose tolerance,insulin sensitivity, and bone density.

Exercise training and intermediate clinical

outcomes

Intermediate outcomes are physiologic mea-sures that are predictive of clinical outcomes inpatients with CHD but are not perceived by the

patients. The best-studied risk-factor predictors

include plasma lipid levels, indices of carbohy-drate metabolism, body weight, body composi-tion, blood pressure, and endothelial function.

Plasma lipid values

Observational studies have demonstrated adirect relationship between the degree of low-

density lipoprotein cholesterol (LDL-C) elevationand high-density lipoprotein cholesterol (HDL-C)reduction and the risk of secondary cardiovascu-lar events [46,47]. Pharmacologic interventional

studies aimed at lowering lipid levels havedocumented a significant reduction in the numberof cardiovascular events and mortality rates in

CHD patients compared with matched controls[48,49]. The effect on lipid parameters of 3 monthsof cardiac rehabilitation without dietary or

pharmacologic intervention is relatively modest[50]. High-density lipoprotein cholesterol levelspredictably increase by approximately 8% to10%, and baseline triglycerides levels above 250

mg/dL decrease by over 20% after conditioning.Exercise conditioning without weight loss fails tolower LDL-C levels significantly. Over the longer

term, HDL-C levels remain increased after re-habilitation to a greater degree in women than inmen [51]. A trial of supervised exercise alone

without medication, dietary modification, orweight loss in patients following coronary bypasssurgery showed no significant differences in lipid

values compared with control patients after 1 year[52].

Exercise training with associated dietary mod-ification, termed comprehensive cardiac rehabili-

tation, has been far more effective than exercisealone in lowering lipid levels [26,30,53]. Ornishet al [30] used a very-low-fat diet and exercise

without lipid lowering medication to assess howlifestyle change impacts lipid levels. At 1 year,they demonstrated a significant decrease in LDL-

C levels associated with insignificant changes inHDL-C and triglyceride levels. These patientsreported a decrease in frequency, duration, and

severity of angina. Schuler [53] and Haskell [26]both used diet and exercise to demonstrate a de-crease in LDL-C and triglyceride levels and bodyweight and an increase in HDL-C level; however

Haskell’s additional use of lipid-lowering agentsdemonstrated more impressive changes in LDL-Cand HDL-C levels. These studies [26,30,53] have

demonstrated the powerful effects of comprehen-sive cardiac rehabilitation on lipid levels, weightreduction, rates of cardiac rehospitalizations,

440 P.A. Ades et al / Cardiol Clin 21 (2003) 435–448

symptoms, and clinical outcomes compared withrandomized controls (Table 1).

Body weight and composition

Obesity has been identified as a significant

independent predictor of cardiovascular disease inboth men and women and as a desirable target forpreventive interventions [54]. Obesity is a highly

prevalent condition among patients with cardio-vascular disease [55]. In a study of 225 cardiacrehabilitation participants in an urban cardiac

rehabilitation program, 48% were found to havea body weight more than 120% of ideal bodyweight [56]. In another review of 730 cardiacrehabilitation participants from the more rural

program at the University of Vermont, 75% wereoverweight with a body mass index (BMI) of morethan 25 kg/m2, and 36% were obese with a BMI

of more than 30 kg/m2 [57]. (The BMI iscalculated as weight in kg/height in m2.)

Visceral obesity, defined as excess intra-

abdominal fat, is particularly linked to a poorcardiac-risk profile. Visceral adiposity is closelylinked to insulin resistance and hyperinsulinemiawith a secondary link to hyperglycemia, hyperlip-

idemia, and hypertension [58,59]. In older womenwith coronary artery disease, the waist circumfer-ence is the best predictor of fasting insulin

concentrations, plasma triglyceride levels, andHDL-C levels [60]. In male patients generalmeasures of obesity such as the BMI and fat

mass better correlate with lipid subfractions [61].Weight loss and exercise are the most effectivenonpharmacologic interventions to improve in-

sulin sensitivity and reduce the associated coro-nary-risk factors. A decrease in the BMI by 3.5kg/m2 is associated with a significant reduction inhyperinsulinemia [62]. Any amount of weight loss

is beneficial; it has been shown that even a 5%weight loss reduces cardiovascular risk factors,and a 10% weight loss improves insulin resistance

and control of hypertension, the lipid profile, andclotting abnormalities [59,63].

Methods of weight loss in cardiac rehabilita-

tion include a decrease in caloric intake and anincrease in exercise-related caloric expenditure. Ithas been recently demonstrated that a behavioral

weight-loss program instituted in the cardiacrehabilitation setting can assist CHD patients inaccomplishing short-term weight loss, with asso-ciated improvement in selected cardiac risk factors

[64]. With a strategy of daily caloric goals,patients self-monitor and record daily caloric

intake and learn behavioral techniques to limitcaloric intake [65].

A complementary option for weight loss

involves an increase in energy expenditure. Sur-prisingly, standard cardiac rehabilitation is as-sociated with only trivial improvements in bodycomposition and weight [66,67]. In traditional

cardiac rehabilitation, obese patients lose less than1 kg after 12 weeks of supervised exercise [50,68].In a preliminary trial of high-caloric exercise in

CHD patients, participants were counseled towalk for up to 20 miles weekly for 4 months inassociation with an isocaloric diet. A significant

weight loss of 4.6 kg occurred in association withrisk-factor improvements [69]. Thus, combiningthe modalities of increased caloric expenditureand decreased caloric intake may be the optimal

approach to weight loss.

Carbohydrate metabolism

Abnormal carbohydrate metabolism (insulinresistance) is an independent risk factor for thedevelopment of coronary heart disease [70]. Ahigh proportion of patients with coronary heart

disease suffer from adult-onset diabetes witha prevalence of 16% to 40% documented incardiac rehabilitation programs [56,71]. Insulin

resistance places a patient at higher risk of deathand reinfarction following an initial coronaryevent [72].

Insulin resistance is associated with vascularsmooth muscle proliferation, elevated plasmino-gen activator inhibitor activity, and a disruptionof normal endothelium [73]. In CHD patients

insulin resistance is usually associated withsyndrome X, manifest by a combination ofhypertension, hyperglycemia, low HDL-C levels,

high triglyceride levels, and clotting abnormali-ties. Weight loss and exercise have been shown todiminish the insulin resistance of this syndrome,

thus reducing cardiac risk factors [59]. A random-ized, controlled trial consisting of moderateexercise and a high-fruit and -vegetable diet for

3 years demonstrated significantly lower insulinlevels, lower pre- and postprandial glucose mea-sures, weight loss, decreased blood pressure,improved lipid profiles, and lower cardiovascular

morbidity and mortality [74]. Clearly, a compre-hensive approach is indicated with weight loss,diet, and exercise playing important roles in

normalizing insulin levels and glycemia, therebyimproving risk-factor profiles and minimizingmedication use.

441P.A. Ades et al / Cardiol Clin 21 (2003) 435–448

Blood pressure

Hypertension is a well-established risk factorfor the development and progression of coronaryartery disease, cerebrovascular disease, renovascu-

lar disease, and chronic heart failure [75]. Thesatisfactory control of elevated blood pressureconstitutes an important goal in the treatment ofpatients with known CHD. Several randomized,

controlled trials have confirmed that exercisetraining lowers blood pressure at rest and duringsubmaximal exercise in both normotensive and

hypertensive individuals to a modest degree[76,77]. In coronary patients, some studies ofexercise and dietary modification have demon-

strated a modest benefit with reductions in systolicand diastolic blood pressures [26], whereas othertrials have failed to demonstrate an overall benefit[76–78]. This lack of effect may be related, in part,

to the fact that most of these studies wereperformed in normotensive persons whose bloodpressure would not be expected to fall substantially

in response to an exercise program. The majorvalue of cardiac rehabilitation in relation to controlof hypertension may lie in the heightened level of

surveillance of blood pressure measures to assist inits diagnosis and its management by lifestylechanges or antihypertensive medications [1].

Endothelial function

When the vascular endothelium is intact, the

normal response to shear stress or acetylcholine isnitric oxide–mediated vasodilation. The endothe-lium also regulates platelet activity, mediatesthrombosis, and limits vascular inflammation

[79]. In the presence of coronary risk factors, nor-mal vasodilation does not occur, and this abnor-mality predicts adverse coronary events [80].

Ludmer [81] has established that endothelialdysfunction is linked to an impedance of coronaryflow, in that that the infusion of an endothelium-

releasing factor agonist (acetylcholine) vasodilatesnormal coronary arteries but paradoxically con-stricts atherosclerotic or otherwise damaged

arteries.Hambrecht et al [82] demonstrated that exer-

cise training in patients with established CHDimproves endothelial function. In a randomized,

controlled trial, patients with endothelial dysfunc-tion characterized by an abnormal vasoconstric-tive response to acetylcholine participated in 4

weeks of aerobic exercise. After 4 weeks, thesepatients demonstrated a diminished constrictorresponse to acetylcholine as compared with the

control group. After exercise, coronary artery con-striction was reduced, correlating with a greaterblood flow velocity. A vasodilatory response waspresent with endothelium-dependent acetylcho-

line, whereas there was no vasodilatoryresponse with endothelium-independent nitroglyc-erine [82].

Exercise improves endothelial function, flow-dependent vasodilation, and blood flow velocityand reserve in other ways. Shear stress augments

nitric oxide synthetase [83], which subsequentlyincreases the synthesis of nitric oxide, causingrelaxation of vascular smooth muscle. Shear stress

is also correlated with augmentation of glutathi-one peroxidase, which protects against hydrogenperoxide, thus preventing oxidative stress andatherosclerosis. Finally, shear stress inhibits ACE

expression [84]. With ACE inhibition, there isultimately a decrease in the production of thepotent vasoconstrictor angiotensin II, with an

associated inhibited degradation of bradykinin.This reciprocal increase in bradykinin augmentsblood flow because of its enhanced vasodilatory

capacity [85]. Multiple cardiac risk factors havebeen demonstrated to be associated with endo-thelial dysfunction. Elevated total cholesterol and

LDL-C levels, increased mental stress, hypergly-cemia, and smoking have all been shown to havenegative effects on coronary endothelium[79,86,87]. With modification of these risk factors,

normal endothelial function can be preserved.

Exercise training and quality-of-life outcomes

The individual’s perception of satisfaction withlife and general sense of well being is a multidi-

mensional concept that has gained acceptance asan important outcome measure in cardiovascularmedicine. It is most commonly measured by

questionnaire, thereby focusing on the patient’spoint of view. Although multiple domains areincluded in the assessment of quality of life, themost commonly described are physical function,

psychologic well-being, and social functioning[88]. Physical function includes the patient’scapacity to perform self-care home activities

and to be physically active and mobile. Psycho-logic well-being includes measures of anxiety,depression, optimism, and self-esteem. Social

functioning includes vocational and social perfor-mance, material welfare, and interaction withfriends and family. Commonly used generalhealth surveys of quality of life include the

Medical Outcomes Study SF-36 questionnaire,

442 P.A. Ades et al / Cardiol Clin 21 (2003) 435–448

the Nottingham Health Profile, and the SicknessImpact Profile [88–90]. Disease-specific instru-ments for cardiac patients include the Minnesota

Living with Heart Failure Questionnaire, theSeattle Angina Questionnaire, and the Quality ofLife after Myocardial Infarction Questionnaire[91–93].

An improvement of quality of life has beendemonstrated in patients who have completeda program that includes education and counseling

in addition to exercise training [31]. Improvementof quality of life has also been seen after re-habilitation in CHD patients following coronary

bypass surgery [22,52], in patients who have acutemyocardial infarction [93,94] and diabetes [95], inelderly women [31], the obese [68], the depressed[96], and among the general population with

coronary disease [97]. One limitation in almostall these studies is that the changes in quality of lifewere not compared with a randomized control

group, raising the concern that the measuredimprovement could have been, at least in part,the natural recovery after a coronary event. A

randomized, controlled trial of exercise rehabilita-tion in patients with chronic heart failure docu-mented an improvement in quality of life after 1

year of exercise [16]. A randomized study of theeffects of 8 weeks of exercise training aftermyocardial infarction in patients with evidence ofanxiety or depression showed a small but signifi-

cant improvement in quality of life [93], althoughthis difference was no longer significant at 1 year.

A high rate of mental depression early after an

acute coronary event has recently been demon-strated, with 30% to 45% of patients sufferingsignificant depressive symptoms [98,99]. Measur-

ing psychosocial variables in patients with coro-nary artery disease is important, because mentaldepression and social isolation have been associ-ated with an increased mortality rate [8]. The

incidence of depression seems to be higher inwomen, obese patients, the elderly, and diabetics[96]. Cardiac rehabilitation in these groups of

people has been shown to be associated withsignificant improvements in quality-of-life, de-pression, anxiety, and somatization scores; how-

ever, these studies generally lacked control groups[96]. Prospective studies have shown that in twothirds of the 20% of patients with signs of

depression symptoms resolved by the end of the3-month period of exercise training [96].

Participation in a cardiac rehabilitation pro-gram after undergoing coronary artery bypass

grafting positively influences the patient’s percep-

tion of health and overall life situation. The effectsare present even as long as 5 years after the eventand have been associated with a tendency to

a higher return-to-work rate [100]. In a random-ized, controlled trial of relaxation training duringcardiac rehabilitation, total coronary events(death, infarction, bypass surgery, and cardiac

hospitalizations) were decreased in the interven-tion group when measured 5 years after rehabil-itation [101].

Physical functioning

Physical functioning was assessed before andafter cardiac rehabilitation in more than 300

consecutive patients enrolled in a cardiac re-habilitation program [102]. A low functionalcapacity at baseline was seen in women, the

elderly, those with a low exercise capacitymeasured on the treadmill, and in the presenceof other chronic medical comorbidities and higherdepression scores (Fig. 2). All patients, particu-

larly those with the lowest baseline scores,improved their perceived ability to performphysical activities. The best predictor of an

enhanced physical function score following re-habilitation was a change in the depression score,followed by change in exercise capacity [102].

Cardiac rehabilitation participation andcompliance

Although cardiac rehabilitation participation

is associated with improved clinical outcomes,relatively few patients have access to suchprograms, and only 10% to 20% of eligible

patients participate in cardiac rehabilitation [1].The best predictor of cardiac rehabilitationparticipation is the strength of the primaryphysician’s recommendation for participation

(Fig. 3) [103]. Significant predictors of lack ofparticipation include a denial of illness severity,a history of mental depression, long travel time,

female gender [103], and inconvenient schedulingtimes [104]. Furthermore, rehabilitation programsare not available in many localities, and patients

are unlikely to drive to a remote program. Arecent review of the Minnesota Heart SurveyRegistry of 3841 patients provides additional

information regarding participation. Patientswho underwent revascularization procedures (sur-gical bypass grafting or percutaneous angioplasty)were more likely to participate than patients who

did not undergo these procedures. Patients who

443P.A. Ades et al / Cardiol Clin 21 (2003) 435–448

Fig. 2. Physical function before and after cardiac rehabilitation stratified by gender and age. Scaled from 0 to 100 with

100 equaling excellent function. Lighter, before rehabilitation; darker, after rehabilitation; *, P<0.05 versus

prerehabilitation. (Adapted from Ades P, Maloney A, Savage P, et al. Physical function in coronary patients: effect of

cardiac rehabilitation. Arch Intern Med 1999;159:2357–60; with permission.)

experienced a myocardial infarction were morelikely to participate than patients diagnosed with

unstable angina [105]. Angina, in fact, is a pre-dictor of noncompliance [106].

For the 10 to 20% of eligible patients who do

participate in cardiac rehabilitation, only 50%comply with the exercise component after 1 year[107]. This statistic compares with a 64% adher-ence to antihypertensive medications at 1 year

[108] and an 82% compliance with lipid-loweringagents at 1 year [109].

Because of the low entry rates and significantdropout rates reflecting travel distance and lack of

transportation, home-based cardiac rehabilitationhas been encouraged and expanded. Home-basedcardiac rehabilitation is directed to all but the

highest-risk patients and incorporates risk-factortreatment along with exercise. Patients who talkedto a nurse by telephone during home exercisesessions showed improvements in aerobic capac-

ity, peak workload, and quality-of-life scoresimilar to those seen in women participating in

Fig. 3. Cardiac rehabilitation participation predicted by physician recommendation score. Recommendation score

scaled from 1 to 5 where 1 equals not mentioned or recommended against, and 5 equals strongly recommended. (From

Ades PA, Waldmann ML, McCann W, et al. Predictors of cardiac rehabilitation participation in older coronary

patients. Arch Intern Med 1992;152:1033–5; with permission.)

444 P.A. Ades et al / Cardiol Clin 21 (2003) 435–448

traditional cardiac rehabilitation [110]. Otherstudies demonstrated that home and grouptraining are similarly effective in increasing

functional capacity after a myocardial infarction[111]. In a study comparing traditional cardiacrehabilitation with a modified off-site version thatpromotes compliance, the off-site version had

significantly increased rates of long-term compli-ance and a significant cost savings [112]. Sugges-tions have been made to improve patient

attendance by offering a transportation serviceor by scheduling convenient program times. Othermethods include signed contracts between the

physician and patient [113,114] and a lower-intensity exercise program [115]. The TrainingLevels Comparison trial, a randomized, controltrial that compared high-intensity and low-

intensity exercise of equal frequency and dura-tion demonstrated that patients are significantlymore likely to adhere to a lower-intensity exercise

program than a high-intensity program [115].

Economic outcomes

The cost effectiveness of cardiac rehabilitation

has been calculated by using data from meta-analyses of randomized studies on survival in the3 years after rehabilitation in postmyocardial

infarction patients [116]. Financial data, hospital-ization costs, and cardiac rehabilitation chargeswere taken from a comprehensive survey of car-diac rehabilitation providers in the United States

and from a study of rehospitalization eventsin the geographic region around Burlington,Vermont [25,116,117]. The cost effectiveness of

cardiac rehabilitation in 1995 dollars was $4900/year of life saved. This cost compares favorablywith other preventive therapies used in the post-

myocardial infarction setting such as phar-macologic lipid lowering, b-adrenergic–blockingmedications, and thrombolysis, although it is less

cost effective than smoking cessation counseling[116]. Exercise rehabilitation studies from theUnited States, Sweden, Norway, and Italy showthat cardiac rehabilitation decreases cardiac re-

hospitalizations [11,16,24–26].

Summary: cardiac rehabilitation as secondary

prevention

The current perspective of cardiac rehabilita-tion is that of a highly structured ‘‘secondary

prevention center’’ with on-site and home exerciseprograms, lipid clinics, weight-loss programs, and

stress-management components aimed at prevent-ing second coronary events and cardiac rehospi-talizations in patients with established coronary

heart disease [1,4,5,118]. The effect of exercise aloneon coronary risk factors, without dietary modifi-cation or medical therapy, is relatively modest [61].When focused risk-factor treatment modules, such

as lipid-lowering clinics or weight-loss programs,are added to cardiac rehabilitation exercise, thebenefits of cardiac rehabilitation are magnified,

and cardiovascular outcomes are improved [119].Comprehensive exercise and risk-reduction pro-grams have been demonstrated to slow the pro-

gression of angiographic disease and to diminishthe rate of recurrent events [26,27]. Expandingbenefits to higher-risk patients who have chronicheart failure, older patients, and, in particular,

older women should maximize the benefits ofcardiac rehabilitation, minimizing coronary dis-ability and preventing coronary events.

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