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Adverse Psychological and Coronary Risk Profiles in Young Patients With Coronary Artery Disease and Benefits of Formal Cardiac Rehabilitation
Carl J. Lavie, MD;
Richard V. Milani, MD
Arch Intern Med. 2006;166:1878-1883.
ABSTRACT
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Background Recent data indicate that young patients with coronary artery disease (CAD) have a poor long-term prognosis. Although the benefits of formal cardiac rehabilitation and exercise training programs are well established, most of these data come from middle-aged and older patients.
Methods We assessed baseline behavioral data, quality of life, and risk profiles in 635 consecutive patients with CAD before and after cardiac rehabilitation and exercise training, and specifically assessed data in 104 young patients (mean ± SD age, 48 ± 6 years; range, 22-54 years) compared with 260 elderly patients (mean ± SD age, 75 ± 3 years; range, 70-85 years).
Results Compared with older patients, young patients had higher body mass indexes (12.2%, P<.001), total cholesterol–high-density lipoprotein ratio (14.6%, P<.01), and triglycerides level (27.2%, P<.01), and a lower high-density lipoprotein cholesterol level (–8.8%, P=.045). Young patients also had higher scores for anxiety and hostility (51.5% and 94.4%, respectively; P<.001 for both), a considerably higher prevalence of anxiety (27.9% vs 13.5%; P<.01) and hostility (12.5% vs 4.6%; P<.01) symptoms, and slightly more depression symptoms (23.1% vs 18.8%) compared with elderly patients. Following cardiac rehabilitation and exercise training, young patients had improvements in body mass index (–1.7%, P<.01), percentage body fat (–4.4%, P<.001), high-density lipoprotein cholesterol level (10.2%, P<.001), high-sensitivity C-reactive protein level (–33.3%, P<.01), peak oxygen consumption (11.3%, P<.001), resting heart rate (–4.5%, P=.01), and resting systolic pressure (–2.3%, P=.049), and marked improvements in scores for depression (–58.5%), anxiety (–46.0%), hostility (–45.7%), somatization (–33.8%), and quality of life (15.8%) (P<.001 for all). Young patients also had greater than 50% to greater than 80% reductions in the prevalence of anxiety (P<.001), hostility (P<.01), and depression (P<.001).
Conclusion These data demonstrate the adverse psychological and CAD risk profiles that are present in young patients with CAD following major CAD events, and are consistent with substantial benefit of formal cardiac rehabilitation and exercise training programs in younger adults.
INTRODUCTION
Substantial evidence indicates that psychological distress is a significant coronary artery disease (CAD) risk factor and adversely affects recovery after major CAD events.1-3 Although most of this evidence has focused on the high prevalence of depression in patients with CAD and on depression as a CAD risk factor,3-6 evidence also indicates that anxiety and hostility are associated with an increase in CAD events.1, 7-15 A psychosocial index comprising many of these behaviors has recently been shown to be an independent risk factor for the development of myocardial infarction.16-17 Moreover, these psychological risk factors have been associated with dyslipidemia, hypertension, obesity, inflammatory biomarkers, coronary calcium and atherosclerosis, and peripheral atherosclerosis.18-23
Although elderly persons compose the largest portion of patients with CAD, recent studies24-27 suggest that younger patients represent a growing segment of the population with CAD and carry a poor long-term prognosis. Researchers28-30 have demonstrated the marked benefits of cardiac rehabilitation and exercise training (CRET) programs in secondary CAD prevention, including benefits on standard CAD risk factors and psychological factors3, 5-6,8, 13-15; however, most of these studies have been performed in middle-aged and older subjects.
The present study determines the baseline psychological and overall CAD risk profiles in many younger patients with CAD and compares them with those of older patients, following a CAD event. We also sought to document the effects of formal phase 2 CRET programs in this young cohort with CAD.
METHODS
STUDY POPULATION
We studied 635 consecutive patients with CAD who were referred to, attended, and completed phase 2 CRET programs at Ochsner Clinic Foundation in New Orleans, following major CAD events (myocardial infarction, unstable angina, or major coronary revascularization), and we specifically assessed detailed data in 104 young patients with CAD (aged <55 years; mean ± SD age, 48 ± 6 years; age range, 22-54 years; 73.1% male) compared with 260 elderly patients (aged  70 years; mean ± SD age, 75 ± 3 years; age range, 70-85 years; 75.4% male). We also report baseline data in 52 young patients (aged <55 years; mean ± SD age, 48 ± 5 years; age range, 23-54 years; 76.9% male) and 68 older patients (aged 70 years; mean ± SD age, 76 ± 4 years; age range, 70-88 years; 67.2% male) who either enrolled and did not attend formal CRET or dropped out during the program. All patients completed validated questionnaires before and after the CRET program. This study was approved by the institutional review board of Ochsner Clinic Foundation.
BEHAVIORAL TESTING
The Kellner Symptom Questionnaire has been validated to assess behavioral characteristics, including symptoms of depression, anxiety, hostility, and somatization, with a lower score indicating a more favorable behavioral trait (manual of the symptom questionnaire available on request; R. P. Kellner, MD, PhD, written and oral communication, 1986).31-32 The Medical Outcomes Study 36-Item Short-Form Health Survey was used to assess the total quality-of-life score using a standardized coding algorithm, with a higher score indicating a more favorable quality of life.33 Based on prior studies of mean scores in healthy subjects (R. P. Kellner, MD, PhD, unpublished data, January 1987, normal scores (scaled score between 1 and 2 SDs above the mean) for anxiety and hostility are 7 or less; and for depression, less than 7. Therefore, we chose 8 or higher as a cutoff to indicate anxiety and hostility symptoms and 7 or higher for depression symptoms. In addition, we assessed the prevalence of these behavioral symptoms in the younger vs the older patients.
PROTOCOL
The protocol, data collection, and statistical analyses were performed as described previously.3, 5-6,8, 13-15 The CRET program generally lasted 12 weeks and consisted of 36 educational and exercise sessions, with exercise sessions consisting of 10 minutes of warm-up, calisthenics, and stretching, followed by 30 to 45 minutes of continuous aerobic and dynamic exercise and light isometrics, and approximately 5 to 10 minutes of cooldown. Exercise intensity was prescribed close to the anaerobic or ventilatory threshold obtained by baseline cardiopulmonary stress testing and 10 to 15 beats/min below the level of any exercise-induced or silent myocardial ischemia. In addition, we encouraged patients to perform 1 to 3 exercise sessions per week at home and periodically adjusted exercise prescription to encourage a gradual improvement in overall exercise performance. Besides the exercise portion of the program, daily lectures and group sessions were directed by a licensed nurse, an exercise physiologist, or a dietitian, emphasizing all aspects of CAD and prevention. Although patients and their significant others were taught about behavioral factors, stress, and sexual function and could ask questions in all of these areas, we did not routinely provide individual attention to these areas, including individual counseling directed at high-risk patients with adverse behavioral characteristics, including anxiety, hostility or anger management, and depression.
At baseline (2-6 weeks after the major CAD event) and again 1 week after the CRET, we obtained several measurements, including height, weight, body mass index, percentage body fat (by the sum of the skinfold method), fasting plasma lipids level, and cardiopulmonary exercise data.
STATISTICAL ANALYSES
Continuous variables were expressed as mean ± SD. Two-sample t tests and analysis of variance were used to assess differences in baseline characteristics and CRET data between young and older patients, and baseline characteristics were also compared between those completing and those not completing the CRET program. Changes between baseline and post-CRET data were compared using a paired t test and  2 analysis, with P<.05 used to determine statistical significance. All data analyses were performed with computer software (StatView; SAS Institute Inc, Cary, NC) on a computer system (Macintosh II; Apple Computers, Inc, Cupertino, Calif).
RESULTS
The baseline characteristics of the study cohort are demonstrated in Table 1. Young CRET patients comprised 16.4% of patients completing the formal program and had a significantly higher body mass index (12.2%), total cholesterol–high-density lipoprotein cholesterol ratio (14.6%), and triglycerides level (27.2%), and lower levels of high-density lipoprotein cholesterol (–8.8%) and resting systolic blood pressure (–7.1%), than elderly patients. As expected, young patients had considerably higher levels of peak oxygen consumption ( O2) (45.7%). In addition, young patients had higher scores for depression (24.2%), hostility (94.4%), and anxiety (51.5%) than did elderly patients and a slightly higher prevalence of depression symptoms and a significantly higher prevalence of anxiety and hostility symptoms (P<.01 for both) than did older patients (Figure). Although many of the baseline characteristics of young patients not completing CRET were slightly more adverse than the characteristics of those completing CRET, only the difference in peak O2 was statistically significant (P=.038). Likewise, elderly patients not completing CRET had significantly lower peak O2 and higher anxiety scores (P=.042 for both) compared with elderly patients completing CRET.
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Table 1. Baseline Characteristics of Young and Older Patients With Coronary Artery Disease, Completing and Not Completing Formal Cardiac Rehabilitation
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Figure. Prevalence of adverse behavioral characteristics in young (mean ± SD age, 48 ± 6 years) and elderly (mean ± SD age, 75 ± 3 years) patients with coronary artery disease at baseline. The asterisk indicates P<.01.
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Following the CRET programs (Table 2), the young patients had significant improvements in many variables, including obesity indexes, high-density lipoprotein level, high-sensitivity C-reactive protein level, peak O2, resting heart rate, and resting systolic pressure. In addition, young patients had marked improvements in scores for anxiety, depression, hostility, somatization, and quality of life.
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Table 2. Risk Factor Changes Noted in 104 Young Patients With Coronary Artery Disease Following Formal Cardiac Rehabilitation*
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Likewise, elderly patients completing CRET also demonstrated significant improvements in most variables studied (Table 3). Although most of the relative improvements following CRET were statistically similar in the younger and older patients, the young patients had significantly greater improvements in body mass index (–1.7% vs –0.4%; P=.03) and hostility score (–45.7% vs –16.7%; P=.05) and a trend for greater improvement in peak O2 (11.3% vs 7.1%; P=.09) compared with the elderly patients. Fasting glucose level decreased minimally following CRET in younger patients and increased significantly in older patients; these relative differences were also statistically significant (P = .03).
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Table 3. Risk Factor Changes Noted in 260 Older Patients With Coronary Artery Disease Following Formal Cardiac Rehabilitation*
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Following CRET, there was a marked decrease in the prevalence of anxiety symptoms (P<.001), with the prevalence of anxiety being equal after CRET in younger and older patients (Table 4). Likewise, the young patients had a greater than 50% decrease in the prevalence of hostility symptoms and a greater than 80% decrease in depression symptoms following CRET.
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Table 4. Effects of Cardiac Rehabilitation and Exercise Training Programs on Symptoms of Anxiety, Hostility,and Depression in Young and Older Patients With Coronary Artery Disease
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COMMENT
There are 3 important findings from this investigation. First, young patients compose a significant segment of the population with CAD completing formal CRET programs. Second, young patients with CAD are characterized by a higher degree of psychological distress, obesity, and dyslipidemia. Third, these adverse characteristics substantially improved following formal phase 2 CRET programs.
The importance of behavioral and psychological risk factors in the pathogenesis and expression of atherosclerosis and CAD has been controversial, although data support the concept that various factors, including depression, anxiety, long-term life stress, and hostility or anger, contribute significantly to the pathogenesis of atherosclerosis and the development of major CAD events.1-23 Probably most of the early evidence focused on depression as a major risk factor.3-6 Moreover, several studies34-35 have demonstrated poor recovery from depression in patients with CAD following major events. In addition to depression, Friedman and Rosenman36 have defined persons who exhibited an emotional syndrome characterized by a continuously harrying sense of time, urgency, aggressiveness, ambitiousness, competitive drive, and easily aroused free-floating hostility as having type A behavior, and some studies7, 9-12 have demonstrated up to a 4-fold increased incidence of clinical CAD in these patients. Recently, hostility has been linked with metabolic syndrome and an increased risk of mortality, especially in younger patients.26-27 The role of anxiety with CAD has been most controversial, although several large-scale community-based studies1, 14, 37 have demonstrated a link between anxiety and cardiac, especially sudden, death. Most important, the INTERHEART study, which included 29 972 subjects from 52 countries, found that psychosocial factors were a strong independent risk factor for myocardial infarction, composing nearly one third of the population's attributable risk for myocardial infarction.16-17
Considerable evidence has demonstrated the substantial benefits of formal phase 2 CRET, including beneficial effects in patients with adverse psychological risk factors.3, 5-6,8, 13-15 In a recent randomized trial, exercise training decreased depressive symptoms as effectively as antidepressant medication in patients with clinical depression.38-39 However, in the field of CRET, most studies have focused on middle-aged or older groups of patients, whereas our study focused on the adverse psychological and overall CAD risk profiles in mostly younger patients following major CAD events. Not only do younger patients experience more obesity and dyslipidemia than do older patients, we also found that the younger patients have a more adverse psychological risk profile, especially hostility and anxiety, that may contribute to the relatively poor prognosis that has been noted in younger patients with CAD.24-26
The mechanism by which psychological and behavioral risk factors may cause premature CAD is unclear, but is likely multifactorial, including worsening atherosclerosis risk factors, as suggested by our data, and may directly contribute to atherosclerosis,8, 18-20 enhanced platelet reactivity,40 inflammation,20 increased catecholamines,41 and coronary vasoreactivity and vasoconstriction,42-43 all of which may increase the risk of CAD events. Anxiety may increase sympathetic activity, reduce vagal tone, and increase the risk of malignant ventricular arrhythmias, all of which may increase the risk of sudden cardiac death.14, 37
The improvements of psychological risk factors noted in our patients following formal CRET are also probably multifactorial. Cardiac rehabilitation is centered around progressive exercise training, which is known to exert salutary effects on certain emotions and autonomic tone.5, 13, 44-45 We have demonstrated that CRET not only improves variables of blood rheology but also has significant benefits for the autonomic nervous system that may be related to the benefits obtained in psychological and behavioral factors.46-47 Recent data also emphasize the beneficial effects of exercise on cognitive function and brain plasticity.48 The education of the patient and the patient's significant other may also be important by increasing understanding of the underlying disease process and its manifestations, thus empowering patients to modify their own recovery. This process of patients becoming more involved in their own health care is called "information involvement,"5, 8, 49 which may enhance the coping and social and emotional recovery process. In addition, socialization and bonding with other patients who are at various stages of recovery and CRET probably contribute to the favorable effects seen on their adverse psychological risk factors.8, 13, 50 Previously, a meta-analysis by Linden et al51 of 23 randomized controlled trials that evaluated the additional impact of psychosocial treatment of rehabilitation demonstrated that this therapy improves psychological distress and biological risk factors (heart rate, systolic pressure, and lipid levels) and reduces major morbidity and mortality. We believe that the benefits obtained in our program are noteworthy, especially because this was accomplished through group sessions for the entire CRET population and individual counseling directed at high-risk behaviors was not included.
Several potential study limitations are worth emphasizing. First, we did not include data on a formal control population. However, in several other studies8, 52 from our CRET programs, including a total of 249 control patients (mostly younger) who did not attend CRET, we identified no improvements over time in the overall CAD risk profile, including behavioral scores and the prevalence of depression, anxiety, and hostility symptoms, which is consistent with other studies34-35 demonstrating poor spontaneous recovery from depression in patients following major CAD events. Therefore, all of this evidence suggests that the improvements noted following CRET are likely secondary to the intervention introduced and not because of chance or regression to the mean. In addition, our patients received dietary recommendations, including increasing consumption of  -3 fatty acids as part of a Mediterranean-type diet, which may have an affect on psychological factors.53 However, patients with and without high psychological risk factors received similar dietary advice, and we did not assess dietary compliance or blood levels of -3 fatty acids. Finally, although the scale that we used for the assessment of behavioral characteristics has been validated,31-32 its prognostic impact has not been as validated as some other scales commonly used. Nevertheless, our prevalence rates of adverse psychological factors, particularly depression, are quite similar to rates published by others using other validated scales.2, 4, 34-37
We believe that our data support the markedly abnormal overall psychological and CAD risk profiles in younger patients with CAD and the substantial benefits that occur following formal CRET programs. Although many young patients with CAD have obstacles to CRET programs, including needing to return to the workforce and family obligations, these data support the need to emphasize formal CRET for their long-term secondary CAD prevention, including routine referral and strongly encouraging young patients to attend and complete these programs.
AUTHOR INFORMATION
Correspondence: Carl J. Lavie, MD, Department of Cardiovascular Diseases, Ochsner Medical Center, 1514 Jefferson Hwy, New Orleans, LA 70121 (clavie{at}ochsner.org).
Accepted for Publication: May 31, 2006.
Author Contributions: Drs Lavie and Milani had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Financial Disclosure: None reported.
Previous Presentation: This study was presented in part as a podium presentation to the Annual Scientific Assembly of the American Heart Association; November 8, 2004; New Orleans, La.
Author Affiliations: Department of Cardiovascular Diseases, Ochsner Medical Center, New Orleans, La.
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