Correspondence
Exercise Capacity and Mortality
N Engl J Med 2002; 347:288-290July 25, 2002
- Article
To the Editor:
Myers et al. (March 14 issue)1 report that in their study, exercise capacity was a stronger predictor of mortality than other established risk factors, after adjustment for several clinical variables. In an earlier article in the Journal, Cole et al. stressed the importance of recovery of the heart rate after exercise; in an analysis adjusted for many confounding variables, a low value for heart-rate recovery, defined as a reduction of 12 beats per minute or less from the heart rate at peak exercise (symptom-limited), was predictive of death from all causes (adjusted relative risk, 2.0; P<0.001).2 The same authors stated that in an analysis adjusted for age and sex, the heart rate at rest, before exercise, was predictive of the risk of death (hazard ratio, 1.29; P<0.001).3
In the group of normal subjects studied by Myers et al., the resting heart rate was much higher in the subjects who died than in those who survived (P<0.001),1 but neither the resting heart rate nor heart-rate recovery after exercise was included in the multivariate regression analysis of mortality. The heart rate, especially during recovery, is a good marker of physical fitness,4 as demonstrated in the study by Cole et al. Thus, it is possible that inclusion of the heart rate as a variable would exclude exercise capacity from the Cox proportional-hazards model in the study by Myers et al. To clarify the respective roles of exercise capacity and heart rate, measured either at rest or after exercise, Myers et al. should reanalyze their data, taking into account this easily measurable variable.
4 ReferencesPaolo Palatini, M.D.
University of Padova, 35128 Padova, Italy
palatini@unipd.it 1
Myers J ,Prakash M ,Froelicher V ,Do D ,Partington S ,Atwood JE . Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002;346:793-801
Full Text | Web of Science | Medline2
Cole CR ,Blackstone EH ,Pashkow FJ ,Snader CE ,Lauer MS . Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 1999;341:1351-1357
Full Text | Web of Science | Medline3
Lauer MS ,Cote CR . Recovery of heart rate after exercise. N Engl J Med 2000;342:662-663
Full Text4
Palatini P ,Julius S . Heart rate and the cardiovascular risk. J Hypertens 1997;15:3-17
CrossRef | Web of Science | Medline
To the Editor:
Myers et al. used Cox proportional-hazards models to determine whether there was an independent association between exercise capacity and mortality. The results of such analyses depend on how the models were developed and particularly on the variables that were considered. However, none of this information is provided.
The authors do not describe the techniques used to develop the predictive models (e.g., stepwise procedures) or the criteria for inclusion or exclusion of variables. They do not state whether variables that were not in the final model — for example, previously established predictors such as obesity1 and heart-rate recovery2 — were considered or excluded. Finally, only limited information is provided on the definitions and coding of coexisting conditions, which can be important sources of confounding. For example, no definition of “mild pulmonary disease” is provided, nor is there information about the specific questions used to determine its presence. Thus, the clinical relevance of the increased risk associated with this variable and how its inclusion in the model may have influenced other estimates are unclear.
2 ReferencesDennis T. Ko, M.D.
Patricia R. Hebert, Ph.D.
Harlan M. Krumholz, M.D.
Yale University School of Medicine, New Haven, CT 065201
Wei M ,Kampert JB ,Barlow CE , et al. Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men. JAMA 1999;282:1547-1553
CrossRef | Web of Science | Medline2
Cole CR ,Blackstone EH ,Pashkow FJ ,Snader CE ,Lauer MS . Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 1999;341:1351-1357
Full Text | Web of Science | Medline
To the Editor:
Balady's editorial1 on the finding by Myers et al. that physical fitness is linked to longevity is thoughtful and informative. However, in the opening paragraph, he suggests the erroneous (albeit enticing) notion that Charles Darwin reached a similar conclusion nearly 150 years ago. The concept of fitness in evolutionary terms has nothing to do with being in shape. Instead, it refers to unintentional, genetically determined adaptation to the environment that leads to success in sexual reproduction. In fact, Darwin argued that modifications in lifestyle are irrelevant in determining the survival of the fittest (and are downright Lamarckian): “with animals, as with plants, any amount of modification in structure can be effected by the accumulation of numerous, slight, and as we must call them accidental, variations, which are in any manner profitable, without exercise or habit having come into play. For no amount of exercise, or habit, or volition, in the utterly sterile members of a community could possibly have affected the structure or instincts of the fertile members, which alone leave descendants.”2 Assuming that the reduction in mortality from all causes in association with exercise, reported by Myers et al., reflects a substantial reduction in cardiovascular events, most people, physically fit or unfit, will have had children before any effect of exercise on survival has been realized.
Dr. Balady's editorial appears in a journal based in the biologic sciences. Therefore, it is of symbolic importance — not only of semantic interest — that his reference to Darwin's theory be clarified.
2 ReferencesDonald H. Perlo, M.D.
17 Gibson Rd., Newton, MA 02460
dhp@world.std. com 1
Balady GJ . Survival of the fittest -- more evidence. N Engl J Med 2002;346:852-854
Full Text | Web of Science | Medline2
Darwin C. On the origin of species: a facsimile of the first edition. Cambridge, Mass.: Harvard University Press, 1975:242.
Author/Editor Response
The authors reply:
To the Editor: Dr. Palatini notes that both the resting heart rate and heart-rate recovery after exercise have been shown to be strong predictors of mortality.1-4 In our study, we addressed the role of both the resting heart rate and heart-rate recovery in predicting mortality. Although the resting heart rate was significantly higher among the subjects who died, it was not independently and significantly associated with the time until death according to a survival analysis. Because of space limitations, we were not able to present all the variables in the model in Table 3 of our article. With regard to heart-rate recovery, in 2001, we reported a study conducted with our data base that focused on this factor.1 Our results were similar to those of other studies in that abnormal heart-rate recovery (which we defined as a reduction of less than 22 beats per minute two minutes after peak exercise) was a strong predictor of death, with a hazard ratio of 2.6 for the comparison with normal recovery. This risk was similar to that associated with low exercise capacity. Subjects with a peak value of less than 5 metabolic equivalents and an abnormal value for heart-rate recovery were at highest risk.
Ko and colleagues are correct in pointing out that any multivariate analysis is highly dependent on model development and the specific variables considered. The manuscript we originally submitted, which included more details about the model, was roughly twice the length of the final manuscript. Most of these details were deleted in order to meet the Journal's maximal word count. We used the term “standardized clinical definitions” to denote generally accepted definitions of risk factors (e.g., for obesity, a body-mass index [the weight in kilograms divided by the square of the height in meters] of 30 or more; for hypercholesterolemia, a cholesterol level that exceeds 220 mg per deciliter; and for mild pulmonary disease, a history of such disease, a forced expiratory volume in one second that is less than 75 percent of the predicted value, or both). Variables were included in the model only if they had previously been established as risk factors for cardiovascular disease or death from all causes.
In terms of model development, the best-performing variables according to univariate analysis were entered into the multivariate model in a stepwise fashion, with pretest variables (historical and risk-factor data) followed by exercise-test data. To keep the model as simple and clinically applicable to an exercise-laboratory setting as possible, detailed electrocardiographic variables in the resting state will be addressed in a separate report. We hope that this information clarifies the questions raised about our analysis of the association between exercise capacity and mortality from all causes.
4 ReferencesJonathan Myers, Ph.D.
Victor Froelicher, M.D.
Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304
drj993@aol.com 1
Shetler K ,Marcus R ,Froelicher VF , et al. Heart rate recovery: validation and methodologic issues. J Am Coll Cardiol 2001;38:1980-1987
CrossRef | Web of Science | Medline2
Cole CR ,Blackstone EH ,Pashkow FJ ,Snader CE ,Lauer MS . Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 1999;341:1351-1357
Full Text | Web of Science | Medline3
Palatini P ,Julius S . Heart rate and the cardiovascular risk. J Hypertens 1997;15:3-17
CrossRef | Web of Science | Medline4
Nishime EO ,Cole CR ,Blackstone EH ,Pashkow FJ ,Lauer MS . Heart rate recovery and exercise treadmill score as predictors of mortality in patients referred for exercise ECG. JAMA 2000;284:1392-1398
CrossRef | Web of Science | Medline
Author/Editor Response
The editorialist replies:
To the Editor: My allusion to Darwin was not meant to misrepresent evolutionary theory; rather, it was meant to extrapolate broadly the concept of survival of the fittest to the contemporary notion of cardiovascular endurance “when fitness is measured and study subjects are followed for years.”1 These words were carefully chosen to highlight the important new data reported by Myers et al., which, added to the growing body of contemporary studies, provide more evidence of a link between higher levels of measured cardiovascular fitness and lower rates of mortality. Dr. Perlo's clarification of the term “fitness,” as viewed by Darwin, is appropriate in order to provide a balanced perspective on these issues.
1 ReferencesGary J. Balady, M.D.
Boston Medical Center, Boston, MA 02118-23931
Balady GJ . Survival of the fittest -- more evidence. N Engl J Med 2002;346:852-854
Full Text | Web of Science | Medline
