Progression of Coronary Artery Disease
A number of studies have investigated the effect of exercise on progression of atherosclerotic disease. The majority of these studies incorporated exercise into a multifaceted intervention, including diet. A significant study reported long-term follow-up of one of these carefully controlled trials of diet and exercise in 113 men with stable CAD.68 The men were randomized to an intensive diet and exercise intervention or limited diet and exercise advice. The exercise group was encouraged to perform 30 minutes of daily cycle ergometer exercise at home and attend at least two supervised 60-minute group exercise sessions weekly. The intervention group improved their physical work capacity by 28%, but the control group remained unchanged. There was no distinction between the two groups in temporal changes in total cholesterol, triglycerides, or body mass index. After 6 years, 66 patients underwent follow-up angiography. Analyzing serial quantitative coronary angiograms on a per-patient basis, these investigators found significantly less progression (59% vs 74%) and significantly more regression (19% vs 0%) in the intervention group compared with the control group.
Finally, the numbers of bone marrow–derived endothelial progenitor cells increase in the peripheral blood of mice and patients with stable CAD subjected to exercise training. Because these cells are thought to exert beneficial effects on vascular repair, angiogenesis, and CAD, much remains to be learned about the fundamental mechanisms underlying the protective and therapeutic benefits of exercise in normal humans and those with CVD.69
Systemic inflammation is emerging as a significant predictor of cardiovascular risk.68 Elevated serum levels of interleukin-6; tumor necrosis factor-α; high-sensitivity C-reactive protein (CRP); and a number of other cytokines, acute-phase reactants, and soluble cytokine receptors have been associated with increased risk of CVD events and diabetes.70,71,72,73 Modest elevation of CRP, in particular, has been associated with CVD risk in observational studies.72 Furthermore, some data support that lowering high sensitivity CRP with hydroxymethylglutaryl–coenzyme A (HMG-CoA) reductase inhibitor therapy reduces risk beyond the benefits accrued from LDL cholesterol lowering alone. Obesity and visceral adiposity are associated with increased levels of CRP, and diet-induced weight loss reduces CRP levels.70 Physical inactivity also correlates with elevated CRP levels in observational studies. Randomized controlled trials examining the effect of exercise on CRP levels are limited.74 Three small, prospective trials of the impact of exercise training on inflammatory markers have enrolled only 104 participants. Two of the three included a control group and showed significantly greater reductions in CRP with exercise training. One small, noncontrolled prospective trial demonstrated a trend toward lower CRP after 6 months of supervised exercise.
Exercise training enhances endothelium-dependent coronary and peripheral arterial vasodilatation in individuals with CAD, peripheral arterial disease, HF, diabetes, and hypertension.71,72,73,75,76 The effect of exercise on vascular function in individuals free of atherosclerotic risk factors has been mixed.77 Exercise’s influence on vascular function appears to be mediated through increased arterial wall shear stress, which promotes enhanced expression and activation of endothelial nitric oxide synthase by means of Akt-dependent phosphorylation.72 In addition to influencing vascular tone, nitric oxide also conveys significant antiatherogenic and antithrombotic effects.78 Exercise also has beneficial effects of thrombotic tendencies and autonomic function in secondary prevention.
The type of exercise has been studied in 209 patients after recent acute infarction. The four groups compared included aerobic training, resistance training, resistance plus aerobic, and no training over a 4-week period. Improved endothelial function was associated with all training modalities, but this effect was no longer seen after 1 month of detraining.79 Additional effects of exercise in secondary prevention are on coagulation, autonomic function, anti-ischemic and antiarrhythmic effects and a decrease in age-related disability.
Exercise in Patients With Heart Failure
There is a daily increase in the millions of people diagnosed with HF, creating a significant impact on the healthcare system. Exercise endurance is limited in these subjects despite advanced drug therapy.80,81 Cardiopulmonary exercise testing is often done to risk stratify HF patients and is readily available in transplant centers. However, the treadmill exercise time with the Naughton protocol, a far simpler test available in a much larger number of hospitals and clinics, provides an inexpensive prognostic screening tool. Based on substantial data, exercise training can improve both cardiac and noncardiac indices.80 Recommendations based on randomized controlled trials encourage exercise training for individuals with HF to impact both functional and symptomatic improvement.82,83 Home-based exercise has been used in 173 subjects with systolic HF. The investigators recorded no differences between the experimental and control groups in the combined clinical end point at 12 months and in functional status, quality of life, or psychological states at 6 months. However, the exercise group had a reduced hospitalization rate (12.8% vs 26.6%; P = .018). Exercise training can improve physiologic indices, including exercise tolerance, ventricular function, skeletal muscle function, peripheral blood flow, endothelial function, diastolic function, and quality of life.83,84 Experience has revealed that exercise in HF is safe and well tolerated if it is appropriately prescribed and augments the benefits of cardiac resynchronization therapy.85,86
The largest and most important trial, Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION), randomized 2331 stable patients (mean age, 59 years; 28% women) with HF and reduced left ventricular ejection fraction (LVEF) to aerobic exercise training (36 supervised sessions followed by home-based training) plus standard pharmacologic treatment versus standard pharmacologic treatment plus usual recommendations regarding physical activity. After a mean follow-up of 2.5 years, there were no statistically significant differences in the primary end point of all-cause mortality and hospitalization (65% exercise training group vs 68% usual care) and secondary end points of mortality (16% vs 17%), CVD mortality, or CVD hospitalization (55% vs 58%) or CVD mortality or HF hospitalization (30% vs 34%). In a prespecified supplemental analysis, adjusting for known major prognostic risk factors in HF (HF cause, exercise duration, LVEF, history of atrial fibrillation or flutter, and the Beck Depression Inventory), the primary end point of all-cause mortality or hospitalization was reduced by 11% in the training group (hazard ratio, 0.89; 95% CI, 0.81-0.99; P = .03).86 CVD mortality or CVD hospitalization was reduced 9% (hazard ratio, 0.91; 95% CI, 0.82-1.01; P = .09), and CVD mortality or HF hospitalization was reduced 15% (hazard ratio, 0.85; 95% CI, 0.74-0.99; P = .03). Because exercise was safe in this patient population in which rates of CVD events, implantable cardioverter-defibrillator firing, and fractures of the hip and pelvis were similar, exercise training of HF patients appears most appropriate.
In the same trial, the health status of the participants was assessed by the Kansas City Cardiomyopathy Questionnaire. There were improvements in the overall summary scale for the exercise group, but also in key subscales, including physical limitations, symptoms, quality of life, and social limitations. Their improvements were considered modest, but significant (P < .001), and add to the overall benefit of the exercise training.84
Components of Contemporary Cardiac Rehabilitation
Historically, cardiac rehabilitation has been arbitrarily divided into successive phases, typically starting during hospitalization for an acute event (Table 106–5). As clinical care and medical economics have evolved, these traditional phases have lost much of their relevance. Contemporary cardiac rehabilitation emphasizes a continuum of care. The American Association of Cardiovascular and Pulmonary Rehabilitation recommends a more descriptive paradigm incorporating three levels of intervention—inpatient, early outpatient, and lifetime cardiac rehabilitation.87,88,89
TABLE 106–5.Phases of Traditional Cardiac Rehabilitation ||Download (.pdf) TABLE 106–5. Phases of Traditional Cardiac Rehabilitation
|Phase ||Location or Timing ||Description ||Duration |
|I || |
Starting as soon as clinically stable
|Gradual progressive activity and introductory education (ie, disease process, cardiovascular symptoms, risk factor management, and lifestyle changes) ||Days |
|II ||Outpatient shortly after discharge ||Multidisciplinary intervention, including progressive exercise, exercise prescription, psychological screening or intervention, smoking cessation, dietary counseling, verification of optimal pharmacologic and device therapy for secondary prevention and functional status, and in-depth education (ie, disease process, risk factor management medications, and weight loss) ||2-12 wk |
|III ||Outpatient immediately after phase II is complete ||Supervised exercise and reinforcement of the principles promulgated during phase II; implementation of progressive exercise prescription; transition to independent exercise venue; can serve as a long-term exercise facility for those lacking alternatives ||6-12 mo, after phase II |
|IV ||Outpatient || |
Focus on adherence to exercise prescription, healthy eating, weight management, tobacco abstinence, medications, and cardiovascular symptom surveillance
The contemporary management of acute coronary syndromes focuses on timely reperfusion, risk stratification, and introduction of proven pharmacotherapy in appropriately selected individuals. The timeline of this intervention has become quite truncated with many patients discharged within 3 days of an acute ST-segment elevation MI. Accordingly, inpatient cardiac rehabilitation has assumed an introductory role. It is focused on early mobilization, starting as soon as patients are hemodynamically stable and free of symptoms of ischemia, arrhythmia, or HF. As the patient progresses to an ECG telemetry environment, progressive ambulation is appropriate, initially with assistance and hemodynamic assessment before, during, and after exercise.
Patients are often unable to assimilate the large amount of information that needs to be introduced. Therefore, the current emphasis is on providing written information for the patient and family, ensuring stable clinical status with activities of daily living, and referring the patient to an appropriate comprehensive cardiac rehabilitation program. In addition, ensuring that patients are discharged from the hospital on appropriate medical therapy is an important part of the initial intervention. A number of practice tools are available to help address the gap between recommended therapy and that which is delivered in practice. Patients are usually more adherent to drug therapy when it is initiated in the inpatient environment.
Early Outpatient Rehabilitation
When formal cardiac rehabilitation programs first evolved in the 1960s and 1970s, the primary concern was the safety of early exercise. As such, ECG telemetry monitoring was incorporated as a means of surveillance for significant arrhythmias. Currently, this monitoring goes beyond telemetry and includes surveillance of symptoms; hemodynamics; glycemic response to exercise (in diabetics); weight; tobacco use; emotional status; and adherence to medications, diet, and home exercise. It also includes review of each individual’s pharmacologic and device therapy to ensure adherence with consensus guidelines. This monitored phase is an intensive, multidisciplinary intervention focused on educating the individual about the disease, its manifestations, and all aspects of its treatment. The goal is to provide each participant with the tools needed to slow disease progression, maintain optimal functional status, and become an informed and active participant in managing his or her condition.
The distinction between traditional phase III (medically supervised) and IV (nonmedically supervised) cardiac rehabilitation has been unclear for some time. Most participants progress to independent exercise without a transitional “phase III.” Nonetheless, some patients are concerned by the prospect of continuing exercise in unfamiliar surroundings and elect to continue exercising at a cardiac rehabilitation facility where they feel safe and are familiar with the personnel, protocol, facilities, and clientele. Clinical features occasionally mandate closer supervision than an unmonitored independent exercise program because of adherence, cognitive limitations, serious comorbidities, hemodynamics, or arrhythmias that require medical supervision during exercise. Unfortunately, continuing cardiac rehabilitation services under such circumstances is generally not reimbursed by third-party payers. Regardless of the venue and the degree of medical surveillance, the goal of this maintenance phase is exercise independence and adherence to exercise prescription, healthy diet, weight management, tobacco abstinence, and medications. For further information, please refer to Chapter 45, Rehabilitation of the Patient with Coronary Heart Disease.