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(Stroke. 2004;35:e79.)
© 2004 American Heart Association, Inc.

Letters to the Editor

Meta-Analysis Reported Incompatible Statistics and Omitted Pertinent Studies

G. David Batty, MSc, PhD

Department of Social Medicine, Panum Institute, University of Copenhagen, Copenhagen, Denmark

Martin J. Shipley, MSc

Department of Epidemiology and Public Health, University College London, London, UK

George Davey Smith, MD

Department of Social Medicine, University of Bristol, Bristol, UK

To the Editor:

The evidence that higher levels of physical activity and cardiorespiratory fitness confer protection against ischemic heart disease (IHD) is persuasive, particularly in middle-¹ and older-aged² men. With the most common type of stroke, ischemic stroke, and ischemic heart disease sharing similar pathophysiological traits, a sedentary existence has been advanced as a lifestyle risk factor for stroke.³ As the cohorts on which the observations of a physical activity–IHD association are based mature, a growing number of publications examining the link between physical exertion and stroke have appeared. The aggregation of results from these studies in the meta-analysis of Lee and others⁴ is therefore timely. However, in our view, the authors reported confusing statistics and omitted some relevant studies.

In Table 3 of their report,⁴ the relative risk (95% CI) of ischemic stroke in the moderate compared with the low active groups is 0.91 (0.80 to 1.05), but this seems incompatible with the reported probability value (P<0.001). Similar observations are made for the hemorrhagic stroke result (RR_{moderate versus low active}; 95 CI: 0.85; 0.64 to 1.13), which has a probability value of 0.001, and for total stroke in a pooling of findings from case-control studies (RR_{high versus low active}: 0.36; 0.25 to 0.52), which has a probability value of 0.04.

Additionally, although the authors’ search strategy was clearly reported, it was not comprehensive. In addition to an electronic search of several medical databases (the authors searched only MEDLINE), scrutiny of the reference sections of relevant articles, contacting experts in the field, and reviewing one’s own files have all been recommended to bolster the number of identified studies.⁵ We are aware of 2 additional reports that appear to meet Lee and others’ inclusion criteria but were omitted from their meta-analysis. In these prospective cohort studies of European populations from the United Kingdom⁶ (362 stroke deaths in 12 552 London-based male civil servants) and Sweden⁷ (111 stroke deaths in 7142 Göteborg men), physical activity was essentially unrelated to total stroke risk at conventional levels of statistical significance.

In the former report from the Whitehall study⁶ we described the relation of physical activity to stroke risk based on a question administered to the first 12 552 study participants in the late 1960s about how much time, if any, they spent walking or cycling to work. Following modification of the study questionnaire during baseline data collection, different inquiries regarding leisure-time physical activity were made to the final 6702 men recruited into the cohort. Although we have previously reported on the relation of IHD and cancer subtypes to this index of physical exertion,⁸ we have yet to examine its predictive capacity for stroke. In new analyses presented here (Table), there were 216 deaths attributed to stroke during 25 years’ surveillance in these men. There was little evidence of an activity-stroke relation, however. We were unable to examine the relation of this index of physical exertion with stroke subtypes because the majority of stroke fatalities were ill-defined on death certificates,⁹ a problem across all UK cohort studies which hold outcome data on deaths.

View this table: [in this window] [in a new window]   Hazards Ratios (95% CIs) for Leisure Time Physical Activities in Relation to Stroke Mortality in the Original Whitehall Study

The omission of these reports notwithstanding, given that inclusion of the total number of stroke deaths from them and the present analyses (n=689) increases the total number of incident stroke reported in Table 1 of the meta-analysis⁴ by around only 14%, the magnitude of the pooled effect estimate for cohort studies with its tight CIs (RR_{high versus low active}; 95% CI: 0.75; 0.69 to 0.82) is unlikely to be markedly attenuated. Therefore, the conclusion of Lee and others⁴ that physical activity is inversely related to total stroke risk is likely to be unaffected.

References

1. Kohl HW III. Physical activity and cardiovascular disease: evidence for a dose response. Med Sci Sports Exerc. 2001; 33: S472–S483.[CrossRef][Medline] [Order article via Infotrieve]
2. Batty GD. Physical activity and coronary heart disease in older adults: a systematic review of epidemiological studies. Eur J Public Health. 2002; 12: 171–176.[Abstract/Free Full Text]
3. Batty GD, Lee IM. Physical activity for preventing strokes. BMJ. 2002; 325: 350–351.[Free Full Text]
4. Lee CD, Folsom AR, Blair SN. Physical activity and stroke risk: a meta-analysis. Stroke. 2003; 34: 2475–2481.[Abstract/Free Full Text]
5. Egger M, Davey Smith G. Principles of and procedures for systematic reviews. In: Egger M, Davey Smith G, Altman D, eds. Systematic Reviews in Health Care: Meta-Analysis in Context. London, UK: BMJ Books; 2001.
6. Batty GD, Shipley M, Marmot M, Davey Smith G. Physical activity and cause-specific mortality in men: further evidence from the Whitehall study. Eur J Epidemiol. 2002; 17: 863–869.
7. Rosengren A, Wilhelmsen AL. Physical activity protects against coronary death and deaths from all causes in middle-aged men. Ann Epidemiol. 1997; 7: 69–75.[CrossRef][Medline] [Order article via Infotrieve]
8. Davey Smith G, Shipley MJ, Batty GD, Morris JN, Marmot M. Physical activity and cause-specific mortality in the Whitehall study. Public Health. 2000; 114: 308–315.[Medline] [Order article via Infotrieve]
9. Strachan D. Ventilatory function as a predictor of stroke. BMJ. 1991; 302: 84–87.[Medline] [Order article via Infotrieve]

Response

Chong Do Lee, EdD

Department of Sports and Exercise Sciences, West Texas A&M University, Canyon, Texas

Aaron R. Folsom, MD

Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, Minnesota

Steven N. Blair, PED

The Cooper Institute, Dallas, Texas

We thank Dr Batty and colleagues for their careful review and comments on our meta-analysis of physical activity and stroke.¹ Indeed, as they pointed out, we unfortunately transcribed 3 probability values incorrectly. The correct probability values for Table 3, testing the null hypothesis of ln(RR)=0, are as follows: ischemic stroke_{low versus moderate}, P=0.09; hemorrhagic stroke_{low versus moderate}, P=0.13; and total stroke (case-control)_{low versus high}, P<0.001. We regret our error but have verified that all other RRs and probability values presented in the article are correct.

Batty and colleagues also pointed out that we omitted 2 cohort studies (the Whitehall study² and the multifactor primary prevention study in Göteborg³) from the analysis. In fact, we had identified but did not include the Whitehall study,² because as we described in our Methods, we included only studies of leisure-time physical activity. The Whitehall study² assessed physical activity as the time spent commuting to work by bicycle or on foot, which we judged not to be leisure-time activity. We somehow did not find the Swedish men’s data,³ and when we added it to the meta-analysis, the results were identical to those in Table 3: RR_{low versus high, cohort}, 95% CI: 0.75, 0.69, 0.82, P<0.001; and RR_{low versus moderate, cohort}, 95% CI: 0.83, 0.76, 0.89, P<0.001.

The overall conclusion of our article was unchanged by correcting the 3 probability values. However, we must correct the conclusion about stroke subtypes to say that moderate levels of physical activity are not clearly associated with reduced risk of ischemic or hemorrhagic strokes, individually, even though high levels of physical activity are.

References

1. Lee CD, Folsom AR, Blair SN. Physical activity and stroke risk: a meta-analysis. Stroke. 2003; 34: 2475–2482.[Abstract/Free Full Text]
2. Batty GD, Shipley MJ, Marmot M, Smith GD. Physical activity and cause-specific mortality in men: further evidence from the Whitehall study. Eur J Epidemiol. 2001; 17: 863–869.[CrossRef][Medline] [Order article via Infotrieve]
3. Rosengren A, Wilhelmsen. Physical activity protects against coronary death and deaths from all causes in middle-aged men: evidence from a 20-year follow-up of the primary prevention study in Göteborg. Ann Epidemiol. 1997; 7: 69–75.[CrossRef][Medline] [Order article via Infotrieve]

This Article Full Text (PDF) All Versions of this Article: 35/4/e79    most recent 01.STR.0000120959.76451.B1v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Batty, G. D. Articles by Blair, S. N. Search for Related Content PubMed PubMed Citation Articles by Batty, G. D. Articles by Blair, S. N. Pubmed/NCBI databases Medline Plus Health Information Exercise for Children Exercise and Physical Fitness Stroke