In a recent meeting with department heads from psychiatry and cardiology, the possibility of hiring a behavioral medicine specialist (e.g. a psychologist) to work exclusively with cardiac and pulmonary patients was discussed. One cardiologist said, “I could probably refer you seven patients every Tuesday.” Whatever clinic he was referring to, it was clear to all in attendance that patients with heart disease very often have behavioral and psychologic concerns that adversely affect patient care, quality of life, and outcomes.
According to the World Health Organization (WHO), one in 500 deaths from cardiovascular disease will die solely because of genetics, but the fate of the rest is not so deterministic. That is, 80–90% of deaths from coronary heart disease (CHD) involve at least one major risk factor influenced by lifestyle. Cardiovascular disease is primarily a disease of lifestyle, and is largely a preventable disease.1 Alcohol/drug abuse, nicotine addiction, anger/hostility, anxiety, depression, chronic stress, cognitive impairment, insomnia, loneliness/social isolation, obesity, and poor patient self-management (i.e. non-adherence to medications, dietary recommendations, exercise prescriptions, and self-care activities) are some of the behavioral and psychological problems encountered routinely by healthcare professionals treating patients with heart disease (see Table 1). These problems create an enormous challenge for cardiologists, who must identify and manage a wide array of behavioral issues, making referrals to behavioral medicine providers where necessary.
Cardiac Rehabilitation for Patients with Behavioral Medicine Needs
Unfortunately, behavioral medicine infrastructure in healthcare is often inadequate and is certainly quite variable across institutions. A referral to a well-staffed psychiatry department or behavioral health service may be easy at some large university-affiliated medical centers, but many cardiologists do not have ready access to behavioral medicine services and must manage things ‘in-house’ or simply send the patient back to a primary care physician for follow-up. Obtaining the right professional referral is preferable, when possible (see Box 1). Furthermore, there is no widely accepted model integrating behavioral medicine services with the practice of cardiology.2 In this article we suggest that outpatient cardiac rehabilitation is an underutilized behavioral medicine resource that is already in place at most medical centers, to which patients can be referred for further assessment and treatment of a variety of behavioral and psychological concerns.
Cardiac rehabilitation is a comprehensive multidisciplinary program that includes supervised, monitored exercise along with extensive patient education and counseling regarding issues such as smoking cessation, nutrition, weight loss, stress management, adherence to preventive medications, and regular aerobic exercise.3 There is good reason to believe that cardiac rehabilitation is a smart move for specific behavioral medicine issues and interventions.
With respect to interventions, cardiac rehabilitation staff are trained in a variety of approaches and have more time to spend with (and alongside) patients than do cardiologists. One good example of evidence-based behavioral treatments is motivational interviewing (see Box 2). Motivational interviewing is a well-known, scientifically tested method of counseling patients that was developed by Miller and Rollnick4 and viewed as a useful intervention strategy in the treatment of lifestyle problems and disease. Motivational interviewing is broadly applicable in the management of diseases that to some extent are associated with behavior. It has been used and evaluated in relation to alcohol abuse, smoking cessation, weight loss, adherence to treatment and follow-up, increasing physical activity, and treatment of diabetes. A meta-analysis showed that motivational interviewing had a significant and clinically relevant effect in approximately three out of four studies, with an equal effect on physiologic (72%) and psychologic (75%) diseases.5 Motivational interviewing in a scientific setting outperforms traditional advice-giving in a broad range of behavioral problems and diseases.5 Although not every cardiac rehabilitation program can provide motivational interviewing interventions, the American Association of CardioVascular and Pulmonary Rehabilitation (AACVPR) has consistently recommended motivational interviewing to its membership and has provided basic training for a number of years at its well-attended annual conferences.
When it comes to specific behavioral medicine issues faced by patients with heart disease, perhaps none is more frequently encountered than depression6–9 (see Box 3). The remainder of this article will focus on depression, as it is an excellent example of how cardiac rehabilitation can be used as part of the continuum of care to address depression while staying consistent with recent American Heart Association (AHA) guidelines on treating depression in patients with heart disease.
Depression in Patients with Heart Disease
Depression is so common that it has been estimated to be the leading cause of disability in the modern world.1 Depression and heart disease co-occur at rates far above chance.10 For example, 15–20% of patients will qualify for a diagnosis of major depressive disorder after a myocardial infarction (MI). ‘Minor depression,’ or clinically significant depression symptoms that do not meet the full diagnostic criteria for major depressive disorder, is also very common among hospitalized patients with heart disease (15–20%). Depression after hospitalization for a cardiac event is not simply caused by the stress associated with a major medical event, as evidenced by the fact that roughly 50% of the patients in the Sertraline and Depression Heart Attack Randomized Trial (SADHART) were already depressed prior to their heart attack.11 Furthermore, many patients continue to experience depression after they have been treated for and recovered from the index event.
Depression and heart disease are likely causally related. Depression has emerged as a possible risk factor for cardiovascular disease, and cardiovascular disease appears to contribute to the development of depression.11–14 Depression has been associated with both an increased risk for developing heart disease and an increased risk for death in patients with heart disease.15 Depression is associated with other risk factors for heart disease, such as smoking,16,17 and contributors to poor outcomes in heart disease, such as medication non-adherence.18,19 Depression and psychologic problems can be underlying issues in some obese patients. Depression also complicates the management of heart disease. For example, it was recently noted that depressed patients with heart failure did not benefit from a disease-management program, in contrast to non-depressed heart failure patients, who appeared to have lower mortality and re-admission for heart failure as a result of the disease-management program.20 In order to be successful, disease-management programs for heart failure may need to specifically address depression when it is present.
Clearly, all cardiologists should be familiar with guidelines for assessing and treating depression. Toward that end, a recent science advisory from the AHA (endorsed by the American Psychiatric Association) recommended routine screening for depression in all patients with heart disease (see Table 2).21 For screening in primary care and other settings, the Patient Health Questionnaire (PHQ)22,23 was recommended.
Of course, brief self-report measures often result in false-positives, and possible cases identified using screening instruments should be verified. For example, if the two-item screening version of the PHQ was used initially, the nine-item version should be administered for confirmation. According to the advisory recommendations, patients scoring >9 on the nine-item version should be evaluated by a professional qualified in the diagnosis and management of depression. Thus, patients who are suspected to have significant depression should be referred for evaluation and treatment, but here the story about ‘what works’ becomes more complicated.
Complexities in the Treatment of Depression in Patients with Heart Disease
Recognition of the link between depression and heart disease stimulated research regarding the treatment of depression in patients with heart disease. In addition to testing therapies for depression, efforts to treat depression in cardiac patients were evaluated for whether or not cardiac outcomes could be improved. The logic was based on a straightforward ‘risk factor reduction’ approach. If depression contributes to risk, an improvement in depression may result in better cardiac outcomes. Unfortunately, psychotherapy and psychopharmacologic treatments have not been shown to reduce mortality or recurrent cardiac events in heart patients.
The first large clinical trial evaluating whether treating depression would reduce mortality following MI was the Enhancing Recovery in Coronary Heart Disease (ENRICHD) trial,24 which enrolled 2,481 patients who were depressed or who reported a low level of perceived social support during the hospitalization that followed their MI. Patients were randomized to treatment as usual or psychologic therapy (cognitive behavioral therapy) supplemented by group therapy and pharmacotherapy for severely depressed patients or those who did not evidence an adequate response. Therapy did improve depression symptoms, but the effect was not much better than that observed for those in the treatment as usual comparison group. Psychotherapy did not reduce the risk for mortality, and it was concluded that cognitive behavioral therapy is effective for depression and improves quality of life,25 but that these effects are modest. Some cases of depression in patients recovering from MI appear to spontaneously remit (at least partially), but patients who failed to improve were at higher risk for eventual mortality.26
Furthermore, self-reported exercise was associated with reduced risk of mortality,27 and the use of selective serotonin re-uptake inhibitors (SSRIs) was associated with reduced mortality.28 Of course, the findings for exercise and SSRIs were not from randomized studies and must be considered suggestive until verified.
SADHART was another large multisite clinical trial of treating depression in patients who had experienced an MI. The SADHART trial enrolled 369 post-MI patients with depression at a number of US and international sites to evaluate use of sertraline in this population.11 The SADHART trial was designed to test the safety and efficacy of sertraline, and was not powered to detect mortality effects. Patients were identified after an MI (or hospitalization for unstable angina), and randomized to 24 weeks of sertraline or placebo (double-blind). Sertraline was found to be safe for cardiac patients, but did not reduce depression symptoms in the full sample. Sertraline was only associated with improvements in depression scores among patients who had previously been depressed. More than half of the patients responded to both sertraline and placebo, again supporting the hypothesis that many patients experience a partial remission in depression symptoms identified at the time of hospitalization. About half of the patients were depressed prior to hospitalization, so elevated depression in-hospital was not merely a due to the psychosocial stress caused by their coronary event. Overall, it appeared that sertraline may be most effective when used with heart patients who have a prior history of depression.
In the Cardiac Arrhythmia Suppression Trial (CAST),29 tricyclic antidepressants were found to be contraindicated for use in heart patients, so it was important to evaluate the safety of newer antidepressants in patients with both depression and heart disease. Patients were identified after an MI (or hospitalization for unstable angina) and randomized in a double-blind fashion to 24 weeks of sertraline or placebo. Sertraline was found to be safe for cardiac patients, but did not reduce depression symptoms in the full sample. Sertraline was associated with improvements in depression scores only among patients who had previously been depressed. More than half of the patients responded to both sertraline and placebo, again supporting the hypothesis that many patients experience a partial remission in depression symptoms identified at the time of hospitalization. About half of the patients were depressed prior to hospitalization, so elevated in-hospital depression was not merely due to the psychosocial stress caused by the coronary event. Overall, it appeared that sertraline may be most effective when used with heart patients who have a prior history of depression.
The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial evaluated citalopram and interpersonal psychotherapy for depression in 284 outpatients with established coronary artery disease and depression.30 Interpersonal psychotherapy is not the same as the cognitive behavioral therapy employed in the ENRICHD trial, although it is also a widely used empirically supported treatment for depression. Patients were randomized to 12 weeks of either interpersonal psychotherapy or clinical management of depression (i.e. usual care) as well as 12 weeks of citalopram or placebo. Citalopram was effective at reducing depression, but interpersonal psychotherapy for depression was no more effective than clinical management among patients with coronary artery disease. The investigators concluded that sertraline or citalopram plus clinical management would be an appropriate treatment approach for patients with heart disease and depression. At this time, interpersonal psychotherapy cannot be recommended for depressed patients who have heart disease, leaving cognitive behavioral therapy as the psychotherapy treatment of choice.
Most recently, results from the Coronary Psychosocial Evaluation Studies (COPES) randomized controlled trial were reported.31 This trial enrolled 157 persistently depressed patients who were randomized to an intervention or usual treatment. The intervention was adapted from the Improving Mood Promoting Access to Collaborative Treatment for late-life depression (IMPACT) study,32 which had shown that an enhanced care approach improved treatment of depression in primary care. In the intervention group, patients were allowed to choose treatments such as antidepressant medication and psychotherapy. The results indicated that this approach substantially reduced depressive symptoms in the intervention group, and that patients receiving the enhanced care also experienced fewer cardiac events during the nine-month follow-up. This trial differs from previous studies in several respects, such as the selection of patients with persistent depression and a more tailored treatment approach that included patient choice. If disseminated, this model may help to resolve the lack of an accepted model of integrating behavioral medicine services with the practice of cardiology.
Additional randomized clinical trials evaluating the treatment of depression among patients with heart disease are under way. The Safety and Efficacy of Sertraline for Depression in Patients with CHF (SADHART-CHF) study will extend the basic rationale of the SADHART study to patients with heart failure and major depressive disorder. A total of 500 patients are expected to be enrolled and randomized to 12 weeks of sertraline or placebo, and a variety of end-points will be assessed, including depression, quality of life, and mortality.
The findings from the SADHART-CHF study should be available soon and are sorely needed, given a report that sertraline was associated with increased risk for mortality or hospitalization among heart failure patients who were not selected on the basis of depression levels;33 that is, among these patients antidepressant use may have been a marker for elevated depression and thus higher risk. Obviously, these data should not be over-interpreted as they are not from a randomized controlled trial of sertraline for depressed patients with heart failure, but the results do underscore the importance of evaluating the safety and efficacy of antidepressants in patients with heart disease.
Current Recommendations and Conclusions Regarding Treatment of Depression in Patients with Heart Disease
With respect to current recommendations for the treatment of depressed patients with heart disease, the AHA science advisory recommended SSRIs, cognitive behavioral therapy, and physical activity such as exercise and cardiac rehabilitation21 (see Table 2). The advisory recommends SSRI treatment on the basis of safety, relatively low cost, and possible effectiveness. By now it should be clear that SSRIs are most likely to reduce depression symptoms among patients with a history of depression. Cognitive behavioral therapy has modest benefits for both reducing depression symptoms and improving perceived social support, but interpersonal therapy for treatment of depression in patients with heart disease cannot be recommended at this time. The recommendation to consider physical activity a treatment option for depression makes outpatient cardiac rehabilitation an attractive referral choice.
What Would Happen for a Depressed Patient During Cardiac Rehabilitation?
Every patient enrolling in outpatient cardiac rehabilitation is screened for depression at intake. This is recommended by the AACVPR,34 is included in the AACVPR/American College of Cardiology (ACC)/AHA 2007 performance measures,35 and is included as part of the psychosocial assessment required by Medicare guidelines. If a patient had screened positive for depression in the cardiology office, that could certainly be noted as part of the referral to ensure that cardiac rehabilitation staff conduct a more thorough assessment.
All patients enrolled in outpatient cardiac rehabilitation engage in a comprehensive intervention program consisting of exercise training, cardiac risk factor modification, and education.36 Following an intake assessment, patients typically attend three sessions of cardiac rehabilitation per week for 12 weeks for a total of 36 sessions. Each patient has an individual, customized exercise plan consisting of warm-up, stretching, exercise on a variety of machines (treadmill, cycling, rowing, stepper, arm crank), and cool-down. The patient’s blood pressure, heart rate, and rhythm are monitored. The education sessions are designed to help patients understand their heart conditions, make healthy lifestyle changes, and promote efforts to prevent future heart problems. Typically, stress management is offered, which has been shown to reduce clinical events independently of exercise.37 Patients typically attend a discharge appointment in which they complete a thorough exit assessment. Throughout cardiac rehabilitation, each patient has a case manager with knowledge of the patient’s circumstances (including depression symptoms) who can monitor depression symptoms over time and serve as a liaison to other services such as cognitive behavioral therapy. Some programs have mental health providers associated with the program, and some have existing relationships with providers at the institution or in the community. Furthermore, patients complete rehabilitation in an encouraging group environment designed to foster mutual support. Most cardiac rehabilitation programs offer long-term maintenance exercise programs to all their patients for as long as the patient wants to continue exercising in this supportive environment; in this way adherence to continued behavior change including depression symptoms can be monitored.
Cardiac Rehabilitation Works
Depressed patients may particularly benefit from participation in cardiac rehabilitation, as they often have lower levels of physical fitness and quality of life,38,39 both of which are targeted during cardiac rehabilitation. In one illustrative study, depressed patients had lower exercise capacity, energy levels, quality of life, and functional status compared with non-depressed patients prior to the start of a rehabilitation program.40 However, after participating in cardiac rehabilitation the depressed patients had marked improvements in depression and quality of life compared with non-depressed patients, in addition to making improvements in exercise capacity, body fat, functional status, energy, and general health ratings.
Patients who complete cardiac rehabilitation tend to experience fewer depressive symptoms at the end of cardiac rehabilitation.41 This is because exercise is a bona fide treatment for depression in both cardiac and non-cardiac samples,42 with similar effect sizes to those observed for antidepressants.43
In addition to the benefit of cardiac rehabilitation for depression and quality of life, it is possible that cardiac rehabilitation could improve prognosis among depressed patients with heart disease. Self-reported regular exercise was associated with a 50% reduction in mortality in the ENRICHD trial.27 Exercise training directly targets modifiable mechanisms that may be implicated in the relationship between depression and cardiac disease. For example, dysregulation of the autonomic nervous system is believed to be involved in the excess risk conferred by depression,44 and cardiac rehabilitation improves markers of autonomic regulation.45 Supporting this argument, it was shown that depressed patients who completed cardiac rehabilitation had 73% lower mortality than patients who did not, and that this was related to physical fitness improvements.46 There are also practical considerations that recommend exercise treatments for depression in patients with heart disease. Some patients perceive mental health treatments to carry a stigma, whereas exercise treatments are well tolerated by patients. Mental health infrastructure is often inadequate at all but the best hospitals and academic medical centers, whereas cardiac rehabilitation is typically available (and underutilized). Of course, depression can be a barrier to enrollment in and completion of cardiac rehabilitation programs,47–54 but this is not surprising because depression appears to reduce adherence to a variety of recommendations and treatments.16,18,19,55–60 Careful case management by a mental health provider may mitigate these concerns.
Future large-scale clinical trials of psychologic and pharmacologic interventions for depression in patients with heart disease will continue to inform practice guidelines. Unfortunately, a randomized controlled trial of exercise for depression in heart disease would be very hard to complete, given the enormous costs of such a study and the ethical dilemma of randomizing some patients to no exercise. In the meantime, cardiac rehabilitation is an excellent option for depressed patients as well as patients struggling with health behavior changes. It works, it improves cardiac outcomes, and it can be combined with other behavioral health interventions as necessary. Here we have argued that depression is a good example of the kinds of psychosocial problem addressed by cardiac rehabilitation. Cardiac rehabilitation is already in place at many medical centers and is staffed with supportive professionals ready to assist patients with their behavioral health needs.