Cognitive Impairment: A New Predictor of Exercise Trainability and Outcomes in Cardiac Rehabilitation?

A cardiac patient is considered to be a poor candidate for an exercise-based rehabilitation program either because coronary disease and/or comorbid conditions limit the ability to exercise vigorously enough to achieve a training effect or because low-level exercise is associated with adverse signs or symptoms (eg, ischemic ST-segment depression [≥1 mm], angina pectoris, threatening ventricular arrhythmias) that are considered potentially dangerous.1 It is helpful to be able to predict which patients will derive substantial physiologic and/or clinical benefits from participation in an exercise training program and which ones will show little or no improvement. The latter, although poor candidates for improved exercise tolerance, may achieve psychological benefits, cardiovascular risk reduction, or ongoing surveillance that improves medical management: outcomes that are vital to their overall rehabilitation. In some cases, patients who are unlikely to profit from a physical conditioning program may be referred for more intensive medical management (such as drug therapy) and considered for cardiac catheterization and coronary revascularization prior to initiation of exercise training. Previous studies have suggested that several variables may influence functional capacity, expressed as metabolic equivalents (METs; 1 MET=3.5 mL O2/kg/min), or the improvement in cardiorespiratory fitness subsequent to regular exercise training. These include initial patient profile and history; clinical cardiac status; left ventricular impairment; response to graded exercise testing; cardioprotective medications; the exercise prescription; time from the acute cardiac event; and patient compliance. Although the extent of exercise-induced cardiovascular improvement among healthy individuals generally shows an inverse relationship with age, habitual physical activity, and initial maximal oxygen consumption (VO2max), in cardiac patients the relationship is more complex. Improvements in exercise capacity may not show an inverse relationship with initial VO2max. Apparently, some patients with low baseline fitness levels are limited because they are deconditioned and thus have great potential to improve, whereas others are limited by residual left ventricular dysfunction, acute myocardial ischemia, the severity of coronary artery disease, and related symptoms (eg, dyspnea on exertion). Habitually sedentary individuals, in particular, should be strongly encouraged to engage in regular exercise so they can move out of the least fit, least active, “high-risk” cohort (bottom 20%).2 Despite demonstration of a significant correlation (r=−0.68) between VO2max and infarct size, the latter has been shown to be a poor predictor of the patient’s VO2max or the ability to improve aerobic capacity with exercise training.3 Moreover, numerous studies have now demonstrated the discordance between resting left ventricular function, aerobic capacity, and exercise trainability.4-6 Although cardiovascular mortality appears to be directly related to the degree of left ventricular dysfunction, the training-induced improvement in aerobic capacity is not necessarily attenuated by a reduced prerehabilitation ejection fraction.7 Poor candidates for exercise training often demonstrate reduced inotropic and/or chronotropic reserve, electrical instability, symptomatic or asymptomatic myocardial ischemia, and a markedly reduced level of cardiorespiratory fitness, adjusted for age and sex. It has been previously suggested that exercise training regimens do not lead to improvements in cardiac patients on β-blockade;8 however, numerous reports have now shown that patients with cardiovascular disease may derive considerable physiologic benefit from an exercise training program in the presence of long-term β-blockade therapy despite therapeutic doses and a reduced training heart rate.9 Improvement in aerobic capacity with exercise training generally shows a positive correlation to the prescribed frequency, intensity, and duration, the latter expressed as minutes per exercise session as well as the length of the training program in weeks or months.1 A marked improvement in VO2max in some studies, despite a relatively low training intensity, suggests that the interrelationship among the training intensity, frequency, and duration may permit a decrease in the intensity to be partially or totally compensated for by increases in the exercise duration or frequency or both. Thus, the improvement in aerobic capacity may depend more on the total amount of exercise accomplished or calories expended than on the specific exercise frequency, intensity, or duration. It also appears that the minimum or threshold intensity for training in coronary patients to enhance the VO2max is lower than previously thought. An analysis of 23 training studies suggested that ∼45% of the oxygen uptake “reserve” (∼69% of maximal heart rate) should be considered the minimal effective intensity for improving cardiorespiratory fitness in this population.10 Finally, lack of improvement with exercise training may be due to intercurrent illness, exacerbation of disease (eg, acute coronary syndrome), injury (eg, orthopedic complications), inadequate adherence to the exercise prescription, poor patient compliance, or combinations thereof. The study by Kakos and colleagues11 published in the current issue of Preventive Cardiology extends these analyses to older adults enrolled in a 3-session-per-week exercise-based cardiac rehabilitation program to determine whether patients with evidence of cognitive dysfunction at baseline may derive less benefit from their course of treatment. Forty-four participants (mean±SD age, 67.6±9.3 years; 29.5% women) were administered a neuropsychological test battery, using the Trail Making Test Part-B (TMT-B) to evaluate cognitive functioning, and the Short Form–36 physical and mental component scales (MCS) to evaluate quality of life before and after a 12-week exercise/education program. All participants also completed the Mini-Mental Status Exam and the Reading subtest from the Wide Range Achievement Test (WRAT-3 Reading Score), to provide additional assessments of cognitive function and reserve. The exercise program consisted of a warm-up, a cool-down, stretching, and a 40-minute, 5-station circuit training regimen using a variety of upper/lower extremity exercise devices at a progressive, escalating, intensity (40%–70% VO2max), based on the patient’s initial physical work capacity, expressed as METs. Cardiorespiratory fitness was determined from a peak or symptom-limited treadmill test, using a ramp protocol, with the achieved METs estimated from the highest treadmill speed, grade, and duration, using previously published equations.12 Participants completed an average of 34.4±8.4 sessions, substantiating a high level of compliance, and demonstrated a significant postconditioning improvement in aerobic capacity (from 7.8 to 10.3 METs) and MCS score (from 49.9 to 54.2). Nevertheless, poorer TMT-B test performance was associated with significantly lower METs and MCS scores at program completion, despite adjustments for age, WRAT-3 Reading Score, and baseline METs and MCS scores. The authors concluded that patients with cognitive impairment may experience reduced benefit from an exercise-based cardiac rehabilitation program, perhaps due to suboptimal adherence to prescribed lifestyle changes, exercise, medications, and/or associated neural responses. It was suggested that cardiac rehabilitation programs consider expanding their baseline functional and risk factor screening to include an assessment of cognitive functioning to help identify patients at greatest risk for poor outcomes. Although the results are unique and provocative, these data should be interpreted with caution in view of the relatively small sample (n=44), the limited number of women (n=13), the short-term nature of the exercise intervention (eg, up to 12 weeks), and the lack of data regarding numerous other potential confounding variables (eg, smoking history, comorbid conditions, medications, body mass index, duration of coronary disease, left ventricular ejection fraction, leisure-time activities). A significant component of age-related dementia, cognitive dysfunction, and Alzheimer’s disease is vascular in origin.13 Others suggest that cardiovascular disease can cause memory lapses and cognitive challenges prior to the onset of stroke or dementia.14-16 Recently, investigators examined the effect of coronary history and duration in 10,308 participants (33% women), aged 35 to 55 years at baseline, on cognitive performance.17 Although time since the first coronary event varied considerably, among men the trend suggested progressively lower scores on reasoning, vocabulary, and semantic fluency among those with longer duration coronary disease. In women, associated cognitive deficits were noted for phonemic and semantic fluency. Silbert and associates18 reported preexisting cognitive impairment in 35% of patients presenting for coronary artery bypass graft surgery, with the most severe deficits occurring for verbal memory learning and executive function. These findings appear to challenge the notion that postoperative cognitive deficit relates directly to the surgical intervention and suggest that it may be associated with poor preexisting cognition. Cognitive impairment is also common among patients with congestive heart failure, with odds ratios ranging from 1.6 to 4.5 (vs matched controls).19-21 The relationship of myocardial infarction severity to deficits in recall and learning suggest that ischemic cardiomyopathy may be a significant factor in the development of cognitive impairment in heart failure.21 Collectively, these data suggest that the severity and duration of cardiovascular disease may be harbingers of cortical derangements in middle-aged and older adults and that risk factor reduction, including dietary modifications and regular exercise,22, 23 may be viable interventions for preventing or favorably modifying age-related cognitive deterioration. The finding that reduced cognitive function portends limited gains in aerobic fitness and poorer outcomes following exercise-based cardiac rehabilitation, as suggested by Kakos and associates, requires additional validation in a larger and more diverse study population. The methodology used to answer this question should also better address the myriad of potential confounding variables as well as the mechanisms that may link cognitive impairment with a diminished benefit from structured secondary prevention. Despite these limitations, this provocative preliminary study, and previous reports,13-21 raise important questions regarding a likely “cognitive-cardiac” vascular connection that is worthy of future investigation.