Cardiac rehabilitation in the elderly Sara K. Pasquali, BS, Karen P. Alexander, MD, and Eric D. Peterson, MD, MPH Durham, NC

Curriculum in Cardiology Cardiac rehabilitation in the elderly Sara K. Pasquali, BS, Karen P. Alexander, MD, and Eric D. Peterson, MD, MPH Durham, NC Background Although patients 65 years old account for the majority of cardiac admissions and procedures in the United States, studies of cardiac rehabilitation have traditionally focused on younger patients. Only recently has the effectiveness of cardiac rehabilitation in the elderly population begun to receive more attention. Methods We present a comprehensive literature review of studies that have looked specifically at the effectiveness of cardiac rehabilitation in the elderly. We discuss the methodologic limitations of studies to date, compare outcomes among elderly rehabilitation patients with those of younger patients, and examine barriers to participation among the elderly. Results The majority of studies published to date have been small observational case series. Despite these limitations, these studies generally show consistent improvements in exercise capacity, cardiac risk factors, and quality-of-life parameters in elderly cardiac rehabilitation patients. These benefits appear to be similar to those seen in younger patients. In spite of this, participation rates among the elderly are low, primarily because of less aggressive referral. Conclusions Although further studies are necessary, the current literature shows that cardiac rehabilitation is associated with improved outcomes after a cardiac event, regardless of age. However, innovative recommendation and referral strategies are needed because few elderly patients actually enroll. (Am Heart J 2001;142:748-55.) Although patients 65 years old account for more than half of all acute myocardial infarctions and coronary bypass operations in the United States, they have generally been underrepresented in cardiovascular clinical research. 1-3 This is particularly true in the field of cardiac rehabilitation, where studies have traditionally focused on patients younger than 65 years. 4 The lack of a clear evidence base has likely played a role in the underreferral of elderly patients to rehabilitation programs. 5 In response to this, several more recent studies have specifically looked at the effectiveness of cardiac rehabilitation in the elderly. 5-22 In this article we review the cardiac rehabilitation literature as it pertains to the elderly population. We will discuss the methodologic limitations of current studies and compare outcomes among elderly patients in rehabilitation with those of younger patients. Finally, we will examine barriers to participation among this age group. From the Outcomes Research and Assessment Group, Duke Clinical Research Institute, Durham, NC. E. D. P. is a Paul Beeson Faculty Scholar, and K. P. A. is a Doris Duke Clinical Research Scientist Awardee. Guest Editor for this manuscript was Frank Aguirre, Prairie Cardiovascular Consultants, Ltd, PO Box 19420, Springfield, IL 62794. Submitted February 16, 2001; accepted July 17, 2001. Reprint requests: Eric D. Peterson, MD, MPH, Division of Cardiology, Duke University Medical Center, Box 3236, Durham, NC 27710. E-mail: peter016@mc.duke.edu Copyright 2001 by Mosby, Inc. 0002-8703/2001/$35.00 + 0 4/1/119134 doi:10.1067/mhj.2001.119134 Benefits of cardiac rehabilitation in younger patients Comprehensive cardiac rehabilitation programs consist of medical screening, cardiac risk factor education, psychosocial support, and exercise training. 4 Over the past 3 decades numerous studies have demonstrated the benefits of cardiac rehabilitation in younger patients. Two metaanalyses done in the late 1980s that looked at >4000 patients from 22 randomized controlled trials showed a 20% to 25% mortality reduction at 3-year follow-up among patients who participated in cardiac rehabilitation after myocardial infarction. 23,24 A more recent meta-analysis of >7000 patients confirmed this mortality benefit. 25 In addition, several randomized controlled trials have shown that cardiac rehabilitation also improves functional capacity, psychologic well-being, overall quality of life, and cardiac risk factors such as lipid profiles and obesity indices. 4,26,27 These improvements are greatest when exercise, risk factor modification, and psychosocial support are provided together in comprehensive programs. 4,26,28 On the basis of this literature, the Clinical Practice Guidelines of the Agency for Health Care Policy and Research, American Heart Association, and American College of Cardiology recommend comprehensive cardiac rehabilitation programs as standard of care after myocardial infarction and revascularization procedures. 4,27 29 Studies of cardiac rehabilitation in the elderly The generalizability of these cardiac rehabilitation recommendations to elderly cardiac patients is unclear.

American Heart Journal Volume 142, Number 5 Pasquali, Alexander, and Peterson 749 Table I. Studies of cardiac rehabilitation comparing outcomes in older and younger patients Relative improvement in elderly vs younger Population Population Compresize age (y) study hensive Functional Risk Study (No. [% elderly])* vs control program capacity factors QOL Observational Williams et al (1985) 6 361 (21%) 65 vs <65 Equal Ades and Grunvald (1990) 7 59 (37%) 62 vs <62 Equal Ades et al (1993) 8 45 (36%) 70 vs 62-70 + Equal Lavie et al (1993) 9 274 (34%) 65 vs <65 Equal Equal Lavie and Milani (1995) 10 458 (43%) 65 vs <65 + Greater Equal Greater Lavie and Milani (1996) 11 283 (19%) >75 vs <60 + Equal Equal Greater McConnell and Laubach (1996) 12 60 (50%) Mean 69.2 vs mean 48.3 Equal McConnell et al (1997) 13 581 (19%) 70 vs <70 Equal Equal Fragnoli-Munn et al (1998) 14 45 (42%) 62 vs <60 + Equal Lavie and Milani (2000) 15 182 (31%) >70 vs <55 + Less Greater McConnell et al (2000) 16 344 (35%) >70 vs 50-69 Equal Equal QOL, Quality of life; Equal, elderly and younger patients show similar improvements in all outcome measures;, no data available; Greater, compared with younger patients, elderly patients show significantly greater improvement in one or more outcome measures; Less, compared to younger patients, elderly patients show significantly less improvement in one or more outcome measures. *Elderly as defined within each study. Obesity indices and lipid profiles. Table II. Studies of cardiac rehabilitation comparing subgroups of elderly patients Population Population age (y) Comprehensive Study size (No.) (study vs control) program Observational Ades et al (1992) 17 226 62 (women vs men) + Lavie and Milani (1997) 18 644 >65 (women vs men) + Milani and Lavie (1998) 19 268 65 (depressed vs nondepressed) + Ades et al (1992) 5 226 62 (nonparticipants vs participants) + Controlled trial Bondestam et al (1995) 20 190 65 (cardiac rehab vs usual care) + Ades et al (1995) 21 83 62 (cardiac rehab vs usual care) Randomized controlled trial Stahle et al (1999) 22 101 65 (cardiac rehab vs usual care) rehab, Rehabilitation. Because of their lower functional capacity and high rate of depression and social isolation, elderly patients may gain the most from comprehensive rehabilitation programs. 10,14,30-34 On the other hand, comorbidities such as arthritis, peripheral vascular disease, and chronic pulmonary disease or the cardiovascular changes that come with age may limit the benefits of cardiac rehabilitation in this age group. 35-37 Unfortunately, only 2 of the 22 studies included in the meta-analyses included any patients >65 years old and none of the studies included patients >70 years old. 23,24 Therefore subgroup analysis from the randomized trial data is not possible. In response to this paucity of information, several recent studies have specifically looked at the effectiveness of cardiac rehabilitation in elderly populations (Table I and II). Below, we comment on methodologic issues in these elderly-specific trials. We also review the conclusions regarding the effectiveness of cardiac rehabilitation in the elderly. Methodologic issues The 18 elderly-specific studies of cardiac rehabilitation are summarized in Tables I and II. In terms of design, the majority of these studies are observational case series, comparing older and younger cohorts of patients in cardiac rehabilitation, without including a nonexercising control group. 5-19 While 2 other studies had a control group but were not randomized, only one study was both randomized and controlled. 20-22 The lack of nonexercising controls prevents a true evalua-

750 Pasquali, Alexander, and Peterson American Heart Journal November 2001 tion of the incremental benefit of cardiac rehabilitation within the elderly population, and the lack of randomization introduces significant participation biases. Those elderly who elect to participate are likely to be healthier and more fit at baseline. In terms of size, the majority are single-center studies. 5,7,8,11-22 Only 2 studies enrolled >500 patients, with the median sample size being 226 total patients. 13,18 On average, elderly patients represented only approximately one third of the total patient population in these studies. When comparing outcomes among older and younger patients in their analysis, none of the studies adjusted for baseline differences in clinical characteristics, functional status, or other factors. This would be particularly important given the nonrandomized design. In addition, the variable definitions of elderly (ranging from 62 to 75 years), the study population (often including combinations of patients with myocardial infarction, bypass grafting, or percutaneous intervention), treatment (exercise only vs comprehensive rehabilitation), and outcomes (eg, exercise capacity as VO 2max, estimated peak aerobic capacity, or treadmill duration) across these studies makes comparison of results challenging. However, despite these limitations, consistent findings can be gleaned regarding the relative impact of cardiac rehabilitation in younger and older patients, which we outline below. Outcomes Morbidity and mortality. Published studies that have included elderly patients are not powered to assess whether participation in cardiac rehabilitation confers a mortality benefit. 5-22 However, one study found that cardiac rehabilitation does reduce morbidity in the elderly, with a lower incidence of rehospitalization at 3 months (13% vs 29%, P <.04) and 1 year compared with control subjects. 20 Cardiac rehabilitation has been shown to be extremely safe, with a multicenter report of >140 US programs documenting a mortality rate of 1 per 784,000 patienthours. 38 However, the applicability of this data to the elderly is uncertain because ages of participants were not reported. It is known that no fatalities among patients participating in cardiac rehabilitation have been reported in the 18 elderly-specific studies. 5-22 Functional status. Functional capacity is usually assessed through a treadmill exercise tolerance test, and reported as peak aerobic capacity (VO 2max, on the basis of measurements of expired gas) or estimated exercise capacity (METs, a multiple of resting energy expenditure calculated from standard formulas based on work load and exercise time). 39 At baseline, elderly patients are significantly less fit, having lower measured (VO 2max, 19% to 30%) and estimated (METs, 27% to 42%) exercise capacity than younger patients. 7-10,15 In spite of this, observational studies have shown significant improvements in VO 2max (+13% to +27%), estimated exercise capacity (METs, +32% to +43%), and treadmill duration (+62%) in elderly patients after cardiac rehabilitation. 6-11 Importantly, the improvement in functional status indicators was of similar magnitude in both young and old patients and was evident even in the very elderly ( 75 years old) (Table I, Figure 1). 6-11 In 2 studies with nonexercising controls, elderly patients in cardiac rehabilitation had significantly greater increases in measured maximal exercise capacity (+17% vs +3%, P <.001) and treadmill duration (+47% vs 8%, P <.001) but not in VO 2max (+16% vs +7%, P not significant) after 3 months of training. 21,22 In one study, this benefit was still present at 1 year follow-up in a subset of patients who continued to exercise for an additional 9 months. 21 In contrast, the benefit was no longer significant in the other study where a group of patients exercised for an additional 3 months, so the duration of training necessary for durable longterm effects is unknown. 22 Even less is known about improving strength through resistance training in elderly cardiac patients. In one observational study, elderly men and women significantly improved leg (+35%) and arm (+14%) strength to a degree similar to that of younger patients after a resistance training program (Table I). 14 This is important because even activities classically considered aerobic, such as walking, are limited by leg strength in elderly patients. 40 Risk factor modification. As in younger patients, cardiac rehabilitation modestly improves risk factor profiles in the elderly population. After 3 months of comprehensive rehabilitation, limited improvements are seen in obesity indices such as body mass index (~ 1%) and percent body fat (~ 6%) in the elderly (Table I, Figure 2). 9-11 In addition, lipid profiles, including high-density lipoprotein (~+5%) and the low-density lipoprotein/high-density lipoprotein ratio, (~ 7%) also modestly improve (Table I, Figure 3). 9-11 Resting systolic blood pressure and plasma glucose levels in elderly patients do not seem to change. 6,8,11 Interestingly, neither the rehabilitation patients nor control subjects in the 2 controlled trials showed any improvements in weight or blood pressure. 21,22 In addition, lipid parameters did not improve in either group. 22 It should be noted that these trials tested an exerciseonly intervention as opposed to a comprehensive program. It is likely that improving risk factor profiles in elderly patients, whether in the setting of cardiac rehabilitation or usual medical care, requires combining exercise, diet modification, and risk factor education, as previously documented in younger patients. 4,26,28 Psychosocial aspects. Type-A behavior, depres-

American Heart Journal Volume 142, Number 5 Pasquali, Alexander, and Peterson 751 Figure 1 Estimated aerobic capacity before and after 3 months of cardiac rehabilitation in older and younger patients. In all 4 studies, elderly patients had significantly lower estimated aerobic capacity at baseline. All cohorts showed significant improvements after rehabilitation. In the 1995 study of Lavie and Milani, 10 the improvement was statistically greater in older versus younger (+43% vs +32%, P <.01). There were similar improvements in older versus younger (P not significant) in the other 3 studies. Figure 2 Percent body fat before and after 3 months of cardiac rehabilitation in older and younger patients. Older and younger patients were similar at baseline. All cohorts showed a significant decrease after rehabilitation, except for the elderly cohort in the 1996 study of Lavie and Milani 11 ( 7%, P =.13). The decrease in percent body fat was statistically similar between older and younger cohorts in all studies.

752 Pasquali, Alexander, and Peterson American Heart Journal November 2001 Figure 3 The low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio before and after 3 months of cardiac rehabilitation in older and younger patients. Older and younger patients were similar at baseline, except in the 1995 study of Lavie and Milani, 10 where elderly patients had significantly lower ratios than did younger patients (3.1 vs 3.6, P.01). The ratio decreased significantly in all cohorts after rehabilitation, and this decrease was similar between older and younger patients. sion, and social isolation have all been shown to increase the risk for development of coronary disease, as well as the risk of morbidity and mortality after a cardiac event. 32,33,41 Of elderly patients referred for cardiac rehabilitation in one study, 18% met criteria for clinical depression, as assessed by a validated symptom questionnaire. 19 In this study, other behavioral parameters such as anxiety, somatization, and hostility were also assessed by validated symptom questionnaire, whereas quality of life and its components were assessed with the Medical Outcomes Study Short Form-36. At baseline, depressed patients had significantly lower exercise capacity ( 15%, P =.02) and quality of life ( 21%, P =.0001) and much higher levels of anxiety (+363%), hostility (+392%), and somatization (+76%) compared with nondepressed patients (all P =.0001). After 3 months of cardiac rehabilitation, the depressed subgroup showed significant improvements in exercise capacity (+27%, P =.0001), hostility ( 36%, P =.004), and somatization ( 39%, P =.0001), similar in magnitude to nondepressed patients. Their improvements in anxiety ( 53% vs 25%, P =.01), depression ( 57% vs 7%, P =.001), and total quality of life (+32% vs +16%, P <.0001) were statistically greater. Overall, the incidence of depression decreased by 54%. These findings indicate that, as in the younger population, cardiac rehabilitation is particularly beneficial to elderly patients who are depressed, in terms of both physical and emotional health. Quality of life. Beyond increasing exercise capacity, cardiac rehabilitation also improves overall quality of life in elderly patients. In observational studies, elderly cardiac rehabilitation patients demonstrate significant improvements in aspects of quality of life, as assessed by the Medical Outcomes Study Short Form-36, including mental health (+5%), energy (+18%), general health (+8%), pain (+20%), function (+16%), well-being (+11%), and total quality of life (+13%) (Table I, Figure 4). 10 These improvements were similar to those in younger patients, except for mental health, which was significantly greater in the elderly (+5% vs +2%, P =.05). The one randomized controlled trial that looked at quality of life after cardiac rehabilitation in elderly patients with use of a validated symptom-based questionnaire (Karolinska questionnaire) showed significant improvements in symptoms of shortness of breath ( 28% vs 11%), palpitations ( 12% vs +6%), fitness

American Heart Journal Volume 142, Number 5 Pasquali, Alexander, and Peterson 753 Figure 4 Physical function score, before and after 3 months of rehabilitation in older and younger patients. In both studies elderly patients had a significantly lower score at baseline (34.6 vs 37.5, P =.02 and 30.2 vs 35.4, P <.01). All cohorts improved significantly after rehabilitation, and this improvement was similar between young and old patients. (+20 vs +5%), and physical activity (+45% vs +22%) after 3 months of training (all P <.05). 22 However, no improvement was seen in symptoms of chest pain, daily activity, or self-perceived health. Referral patterns. Although the available evidence indicates that cardiac rehabilitation benefits young and old alike, elderly patients are 1.5 to 2 times less likely to participate in rehabilitation programs. 9,10 For example, a study of patients >62 years old who were hospitalized for acute myocardial infarction or coronary artery bypass surgery at the University of Vermont Medical Center documented a 21% participation rate compared with 42% in younger patients. 5 In this study, patients who participated in rehabilitation were more likely to be younger, male, white collar workers, with more formal education and less chronic disease. Commute time, patient denial of severity of illness, and history of depression were also significant predictors of participation. By multivariate analysis, the strength of the primary physician s referral was the single most powerful predictor of participation, with 2% of elderly patients participating when the recommendation was weak compared with 66% when it was strong. Elderly women tend to have even lower participation rates than elderly men (15% vs 25%, P =.06), primarily related to less physician recommendation. 17 Women also had more transportation problems, were more likely to be widowed or to have a dependent spouse at home, and had more comorbid conditions. These studies suggest that lower participation rates in the elderly are primarily due to lack of physician referral and support the findings of others who have shown that physicians are generally less aggressive in the treatment of cardiovascular disease in women and the elderly. 42-44 Conclusions and future directions At present, we lack a solid base of clinical studies to define the role of cardiac rehabilitation in improving outcomes for elderly cardiac patients. The majority of studies published to date have been small in size and observational, without appropriate controls. Despite these limitations, these studies show consistent improvements in exercise capacity, cardiac risk factors, and psychologic and quality-of-life parameters in elderly cardiac rehabilitation patients. These benefits are similar to those seen in younger patients. In spite of this, participation rates among the elderly are low, primarily because of less aggressive referral. Larger trials are needed to confirm the benefits of car-

754 Pasquali, Alexander, and Peterson American Heart Journal November 2001 diac rehabilitation over usual care in the elderly, as well as to assess long-term outcomes. Because randomization of patients to rehabilitation would be difficult, as it has become the standard of care in the United States, observational studies that control for the natural course of recovery after a cardiac event, as well as differences in baseline functioning, may be more appropriate. In addition, we need better studies to assess the effectiveness of cardiac rehabilitation not only on physical capacity and cardiac risk factors but also on quality of life in the elderly population. Finally, investigating new strategies to encourage participation and improve the referral process is warranted. While awaiting these studies, we believe that the current cardiac rehabilitation guidelines should be applied to elderly cardiac patients, given the consistent positive findings to date. Specifically, we recommend that after an acute myocardial infarction or revascularization procedure all elderly patients who are physically able to participate should receive recommendation and referral to a rehabilitation program from their physicians as this recommendation is a key determinant of subsequent program enrollment. We would like to acknowledge the excellent editorial assistance of Tracey A. Dryden. References 1. American Heart Association. 2000 Heart and stroke statistical update. Dallas (TX): American Heart Association; 1999. 2. Alexander KP, Peterson ED. Coronary artery bypass grafting in the elderly. Am Heart J 1997;134:856-64. 3. Gurwitz JH, Col NF, Avorn J. The exclusion of the elderly and women from clinical trials in acute myocardial infarction. JAMA 1992;268:1417-22. 4. Wenger NK, Froehlicher ES, Smith LK, et al. Cardiac rehabilitation: clinical practice guideline No. 17. 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American Heart Journal Volume 142, Number 5 Pasquali, Alexander, and Peterson 755 (Committee on Management of Acute Myocardial Infarction). Available at: www.acc.org. Accessed on November 28, 2000. 30. Milani RV, Lavie CJ, Cassidy MM. Effects of cardiac rehabilitation and exercise training programs on depression in patients after major coronary events. Am Heart J 1996;132:726-32. 31. Blazer D. Depression in the elderly: myths and misconceptions. Psychiatr Clin North Am 1997;20:111-9. 32. Blazer DG, Kessler RC, McGonagle KA, et al. The prevalence and distribution of major depression in a national community survey: the National Comorbidity Survey. Am J Psychiatry 1994; 151:979-86. 33. Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction: impact on 6-month survival. JAMA 1993; 270:1819-25. 34. Ruberman W, Weinblatt E, Goldberg JD, et al. Psychosocial influences on mortality after myocardial infarction. N Engl J Med 1984; 311:552-9. 35. Ades PA, Waldmann ML, Meyer WL, et al. Skeletal muscle and cardiovascular adaptations to exercise conditioning in older coronary patients. Circulation 1996;94:323-30. 36. Lakatta EG, Mitchell JH, Pomerance A, et al. Human aging: changes in structure and function. J Am Coll Cardiol 1987;10:42-7A. 37. Vaitkevicius PV, Fleg JL, Engel JH, et al. Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation 1993;88: 1456-62. 38. Van Camp ST, Peterson RA. Cardiovascular complications of outpatient cardiac rehabilitation. JAMA 1986;256:1160-4. 39. Bardsley WT, Mavkin HT. Exercise testing. In: Brandenburg RD, Fuster V, Giuliani ER, et al, editors. Cardiology fundamentals and practice. Chicago: Year Book; 1987. p. 369-402. 40. Ades PA, Ballor DL, Ashikaga T, et al. Weight training improves walking endurance in the healthy elderly. Ann Intern Med 1996; 124:568-72. 41. Ariyo AA, Haan M, Tangen CM, et al. Depressive symptoms and risks of coronary heart disease and mortality in elderly Americans. Circulation 2000;102:1773-9. 42. Ayanian JZ, Epstein AM. Differences in the use of procedures between women and men hospitalized for coronary heart disease. N Engl J Med 1991;325:221-5. 43. Tobin JN, Wassertheil-Smoller S, Wexler JP, et al. Sex bias in considering coronary bypass surgery. Ann Intern Med 1987; 107:19-25. 44. Yusef S, Furberg CD. Are we biased in our approach to treating elderly patients with heart disease? Am J Cardiol 1991;68:54-6. Receive tables of contents by E-mail To receive the tables of contents by e-mail, sign up through our web site at http://www. mosby.com/ahj Choose E-mail notification Simply type your e-mail address in the box and click on the subscribe button Alternatively, you may send an e-mail message to majordomo@mosby.com Leave the subject line blank, and type the following as the body of your message: subscribe ahj_toc You will receive an e-mail to confirm that you have been added to the mailing list. Note that TOC e-mails will be sent out when a new issue is posted to the Web site.