Exercise Capacity
2003; Lippincott Williams & Wilkins; Volume: 108; Issue: 13 Linguagem: Catalão
10.1161/01.cir.0000094408.38603.7e
ISSN1524-4539
AutoresDaniel B. Mark, Michael S. Lauer,
Tópico(s)Blood Pressure and Hypertension Studies
ResumoHomeCirculationVol. 108, No. 13Exercise Capacity Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBExercise CapacityThe Prognostic Variable That Doesn't Get Enough Respect Daniel B. Mark and Michael S. Lauer Daniel B. MarkDaniel B. Mark From the Outcomes Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (D.B.M.), and the Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio (M.S.L.) and Michael S. LauerMichael S. Lauer From the Outcomes Research and Assessment Group, Duke Clinical Research Institute, Durham, NC (D.B.M.), and the Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio (M.S.L.) Originally published30 Sep 2003https://doi.org/10.1161/01.CIR.0000094408.38603.7ECirculation. 2003;108:1534–1536Clinicians have long been aware that patients capable of high levels of physical exertion have a better prognosis than those with limited exercise capacity. Although the initial clinical encounter usually suffices to gain a qualitative appreciation of functional capacity, more precision can be obtained from formal graded exercise testing. In both asymptomatic subjects and patients with clinical coronary artery disease (CAD), exercise-based measures of functional capacity repeatedly have been shown to provide powerful independent prognostic information.1,2 Yet when decisions are made about the role and value of exercise testing in clinical cardiology, the focus is inevitably on measures believed to reflect the state of the coronary arterial circulation and the potential need for angiography and revascularization. The widespread tendency to ignore exercise capacity in clinical management seems to be a function of a general uncertainty about its therapeutic implications. Stress-induced ischemia may be less important prognostically, but its message seems clear: Fix the plumbing.See p 1554In symptomatic CAD patients, exercise capacity typically is used to provide the context in which ischemic responses are interpreted.3 Thus, ischemia in the setting of poor exercise capacity means high risk, whereas in the setting of good exercise capacity, ischemia (even when measured with nuclear perfusion techniques) has little prognostic impact.4 In asymptomatic subjects, in whom evidence of ischemia is quite infrequent, the utility of exercise capacity has been more of a puzzle. In the American College of Cardiology/American Heart Association Exercise Testing Guidelines,5 exercise testing for routine screening of asymptomatic men and women was rated a Class III indication (ie, not useful). The use of exercise testing in asymptomatic persons with multiple risk factors as a guide to risk reduction therapy was rated a Class IIb indication (ie, usefulness not well established).6 These recommendations reflect concerns about harm to subjects resulting from false-positive studies when the focus is on identification of CAD.7In the present issue of Circulation, Gulati and colleagues8 examine the prognostic importance of exercise capacity in asymptomatic women. A volunteer cohort of 5721 women aged ≥35 years in the Chicago metropolitan area was enrolled in the St James Women Take Heart (WTH) Project in 1992. Subjects were required to be free of symptomatic cardiovascular disease and able to do a symptom-limited Bruce protocol treadmill test, which was part of the baseline evaluation. Follow-up to the end of 2000 was obtained from the National Death Index. Using the Framingham Risk Score to control for the effect of standard CAD risk factors, the investigators found that peak exercise capacity was a substantial independent prognostic factor in this population. For every 1-MET increase in exercise capacity, the authors projected a 17% decrease in all-cause mortality. Notably, this relationship did not seem to be attributable to incipient preclinical disease because excluding the early deaths (through year 4) did not alter the relationship.The St James WTH study is not the first to examine exercise capacity in asymptomatic women, but it is the largest and provides the most unambiguous evidence to date of its independent prognostic importance. These results are, in fact, quite comparable to those previously obtained in both asymptomatic and symptomatic men.1,9,10 The strong prognostic value of exercise capacity is also evident in elderly men.11 In short, exercise capacity appears to be a remarkably robust and important measure.The publication of this new, carefully done, large-scale epidemiological study provides a good opportunity to take stock of the clinical implications of exercise capacity in 2003. We can do this by considering three issues: (1) What do we know about the therapeutic implications of poor exercise capacity? (2) Must we measure exercise capacity, or will taking a history about physical activity levels suffice? and (3) Do the available data now support a more positive guideline recommendation about exercise testing in asymptomatic subjects?Poor exercise capacity may be caused by ischemia but can also be caused by a host of factors apparently less amenable to "fixing," such as diastolic dysfunction, pulmonary disease, chronotropic incompetence, and general deconditioning. The additional prognostic information provided by exercise capacity can be therapeutically useful in two ways. As a nonmodifiable indicator of risk, similar to age, gender, and genetics, it can direct us to higher-risk groups who need intensification of management. For example, Greenland and colleagues12 proposed that asymptomatic subjects who are deemed to be at intermediate risk on the basis of clinical and demographic factors would be suitable for additional noninvasive testing, such as exercise testing, to help identify high-risk subjects for whom intensive risk factor modification is warranted. In the Coronary Artery Surgery Study,13 high exercise capacity (≥10 METS) was associated with excellent prognosis even in patients with 3-vessel disease, and this subgroup showed no significant benefit from surgery. The benefits of surgery seemed to be confined to the CAD patients with impaired exercise capacity, even among patients with impaired left ventricular function.Poor exercise capacity may also correlate with pathophysiological factors that modify the course of CAD, such as platelet function and autonomic tone. Thus, data from the Cleveland Clinic showed that the prognostic benefits of aspirin therapy in patients with known or suspected CAD were substantially greater in patients who had fair or poor exercise capacity for age.14 In a prospective randomized trial of 4 weeks of endurance training in 95 consecutive survivors of an uncomplicated myocardial infarction, baroreflex sensitivity improved 26% relative to those with no training (reflecting a shift of autonomic activity toward increased vagal tone).15 Over the ensuing 10 years, prognosis was substantially better in the patients who trained and improved their baroreceptor sensitivity relative to those who trained but did not improve (nonresponders) or those randomized to the no-training arm. However, improved baroreceptor sensitivity may itself merely be a marker for some other favorable characteristic responsible for improved prognosis.Conversely, as a modifiable risk factor, poor exercise capacity can specifically indicate the need to improve cardiorespiratory endurance with exercise training. In order to assess whether modifying exercise capacity does, in fact, alter survival in the expected manner, we need randomized trial data. Unfortunately, such data are lacking. However, there are data showing that exercise training can delay the onset of diabetes and improve other risk factors, such as hypertension and hyperlipidemia.16,17 Although the concept of exercise as a therapy has much to recommend it, and increasing activity to improve health has been recommended by the US Surgeon General, the Centers for Disease Control, and the American Heart Association, the evidence that exercise therapy will improve prognosis is inferential. Thus, although subjects who are more active have a better prognosis, we do not know if this is because of the exercise value of their activities or because subjects with better health choose to be more active. Epidemiological data suggest that the major prognostic benefit of exercise is to be obtained by moving out of the lowest 20th to 25th percentile of fitness, with relatively modest prognostic gains from further improvements.18 Whether this observation has implications for the mechanism of prognostic benefit remains unclear. Additionally, getting deconditioned, habitually inactive subjects to significantly improve their fitness is a substantial challenge that falls outside the current purview of most clinicians.Both poor exercise capacity and low levels of self-reported physical activity identify high-risk subsets. Because assessment of physical activity is simpler, inasmuch as it can be done by questionnaire, it would be convenient if this were a sufficient surrogate for poor exercise capacity. Conceptually, physical activity is the process or behavior, and improved exercise capacity (or cardiorespiratory endurance or fitness) the desired result. Because subjects may not elect to do activities that challenge their physical capacity and therefore may not even be aware of their limits, the two measures often do not provide the same information. Furthermore, there are numerous ways to make each measurement, and the method of measurement itself can affect the result obtained. Physical activity is usually assessed by a self-report questionnaire covering a variable time period and level of detail. The assessment may consider leisure time, occupation-related time, or both. Exercise capacity or cardiorespiratory endurance is measured with a cycle ergometer or treadmill, and assessment of fitness relates measured capacity to relevant age and sex norms. Despite these complexities, both types of measures have been shown to provide independent prognostic information in a variety of populations.19 Whereas there is a continuous linear relationship between increasing activity and improved prognosis, the major prognostic gradient for physical fitness, as noted above, seems to be in separating out the most unfit (eg, the bottom 20%) from the remainder.18 In a preliminary multivariable analysis of the Aerobics Center Longitudinal Study data, activity level was not independent when physical fitness and other risk factors were considered.19 However, the degree to which being unfit and being inactive constitute different and complementary risk factors remains unsettled.18 It has been argued that increasing activity will necessarily improve fitness and thus health outcomes, but the desirable dose of activity/exercise remains controversial.The clear implication of the St James WTH study and other similar studies is that improving exercise capacity will improve prognosis. As noted earlier, this important hypothesis has not been adequately tested. No large-scale randomized trials have attempted the challenge, probably because of the large sample required and the logistical problems of getting large groups of couch potatoes to change their behaviors. The two large observational studies in this area found that unfit subjects who became fit over time did in fact have an improved prognosis compared with the persistently unfit.1,20 However, a recent critique of the Aerobics Center Longitudinal study has argued that the apparent improvement could be entirely due to measurement error intrinsic in the assessment of exercise capacity.21The St James WTH study provides us with an opportunity to reconsider whether exercise capacity should be measured in asymptomatic subjects as part of a cardiovascular risk assessment process. The data are now quite persuasive that this measure provides independent prognostic information in both men and women. Making a sharper assessment of risk would be attractive if we can use the additional insights to improve our preventive therapies. Unfortunately, as reviewed above, the available data are still insufficient to tie risk levels related to exercise capacity with any therapeutic intervention at a high level of confidence. It could be argued that there is little harm in a recommendation to screen for the extremely unfit and encourage them into some form of exercise and primary prevention program. However, medicine is littered with examples of the unintended consequences of well-meaning, seemingly innocuous interventions, and one of the contributions of evidence-based medicine is to require that we be honest about what we know versus what we simply believe.Given these considerations, we feel that the St James WTH study and its predecessors have created the equipoise needed for a proper randomized trial. On the basis of these data, we believe that the most efficient strategy for such a trial would be to target asymptomatic subjects at the lowest end of the fitness spectrum. Interventions could be applied in a factorial design to modify cardiovascular risk factors or to improve exercise capacity beyond some nominal threshold. There are dozens of reasons not to do such a trial. It will be difficult to get the experts to agree on the design; it will be expensive; there is no "deep-pocket" commercial company to help pay for it; and there is a risk that at the end of it all the control group will improve as much as the treatment group (the Multiple Risk Factor Intervention Trial [MRFIT] phenomenon). Two factors counterbalance these arguments. First, all the easy randomized trials have already been done. All that remain are the difficult ones. Second, an effective intervention applied to the most unfit members of our society before they develop clinical disease has the upside of a huge potential for improving health and even generating long-term cost savings. Our society invests a great amount of money and resources in halfway technologies to palliate chronic diseases.22 We think that some of that investment needs to be used to develop robust clinical trial evidence on the therapeutic ramifications of one of the most potent prognostic variables we have discovered.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.FootnotesCorrespondence to Daniel B. Mark, MD, MPH, Professor of Medicine, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715. E-mail [email protected]References1 Blair SN, Kohl HW 3rd, Barlow CE, et al. Changes in physical fitness and all-cause mortality: a prospective study of healthy and unhealthy men. JAMA. 1995; 273: 1093–1098.CrossrefMedlineGoogle Scholar2 Snader CE, Marwick TH, Pashkow FJ, et al. Importance of estimated functional capacity as a predictor of all-cause mortality among patients referred for exercise thallium single-photon emission computed tomography: report of 3,400 patients from a single center. J Am Coll Cardiol. 1997; 30: 641–648.CrossrefMedlineGoogle Scholar3 McNeer JF, Margolis JR, Lee KL, et al. The role of the exercise test in the evaluation of patients for ischemic heart disease. Circulation. 1978; 57: 64–70.CrossrefMedlineGoogle Scholar4 Diaz LA, Brunken RC, Blackstone EH, et al. Independent contribution of myocardial perfusion defects to exercise capacity and heart rate recovery for prediction of all-cause mortality in patients with known or suspected coronary heart disease. J Am Coll Cardiol. 2001; 37: 1558–1564.CrossrefMedlineGoogle Scholar5 Gibbons RJ, Balady GJ, Beasley JW, et al. ACC/AHA Guidelines for exercise testing: executive summary. 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Is physical activity or physical fitness more important in defining health benefits? Med Sci Sport Exerc. 2001; 33: S379–S399.CrossrefMedlineGoogle Scholar20 Erikssen G, Liestol K, Bjornholt J, et al. Changes in physical fitness and changes in mortality. Lancet. 1998; 352: 759–762.CrossrefMedlineGoogle Scholar21 Williams PT. The illusion of improved physical fitness and reduced mortality. Med Sci Sports Exerc. 2003; 35: 736–740.CrossrefMedlineGoogle Scholar22 Lewis T. The Lives of a Cell: Notes of a Biology Watcher. New York: Viking Press, 1974.Google Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Lee J, Jeong J, Ji W, Lee H, Lee Y, Jo M, Chung S, Yun S, Choi C, Lee G, Lee S and Lee J (2022) Comparative effectiveness of smartphone healthcare applications for improving quality of life in lung cancer patients: study protocol, BMC Pulmonary Medicine, 10.1186/s12890-022-01970-8, 22:1, Online publication date: 1-Dec-2022. 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