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Cited by 27Physical Activity and HealthAcute Ischemic Stroke ManagementSex and Gender in Healthcare

Sex Differences in Physical Activity and Incident Stroke: A Systematic Review

Open access
Madsen, Tracy E., Samaei, Mehrnoosh, Pikula, Aleksandra, Yu, Amy Y.X., Carcel, Cheryl, Millsaps, Erika, Yalamanchili, Ria Sara, Bencie, Nicole +5 more·2022·Clinical Therapeutics
DOI 10.1016/j.clinthera.2022.02.006PMC PMC9195871
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Abstract

Purpose Physical inactivity, a modifiable risk factor for cardiovascular disease, is independently associated with stroke. Though some prior data have suggested sex differences in levels of physical activity, whether there are sex differences in the role of physical activity in primary stroke prevention is largely unknown. This systematic review identifies and describes recent findings on sex differences in the association between physical activity and incident (first-ever) stroke. This review also describes the current evidence on the strength of the association between physical activity and a reduced stroke risk in women in particular. Methods Using a prespecified strategy, PubMed/MEDLINE and Cochrane Central were searched to identify observational studies or trials published from 2000 to 2020 and reporting sex differences in physical activity and incident stroke. To be included, among other criteria, studies had to include sex-specific effect estimates from women, men, or both. Titles, abstracts, and full-text articles were screened to identify studies meeting the inclusion criteria, and adjusted sex-specific estimates of the association between physical activity and incident stroke for total stroke (ischemic plus hemorrhagic) or ischemic stroke were abstracted. Findings Thirty-seven studies met the inclusion criteria. Of 17 studies that included data on total incident stroke (ischemic and hemorrhagic combined) in both women and men, 7 (41%) showed similar associations between physical activity and incident stroke between women and men, 6 (35%) suggested a significant effect in women but not in men, and 3 (18%) showed a significant effect in men but not in women. Of 10 studies that included data on ischemic stroke in women and men, 5 (50%) suggested similar effects in women and men, 4 (40%) suggested a significant effect in women but not in men, and 1 (10%) showed an effect in men but not women. In women specifically, the majority of included studies demonstrated a reduced risk for incident stroke with physical activity, with relative risk reductions ranging from 11% to 72%, though most estimates fell between 20% and 40%. Implications The majority of studies indicated a clear association between physical activity and a reduction in stroke risk. Studies were split as to the potential for sex differences in this association. Future prospective investigations should identify strategies for the use of increased physical activity for primary stroke prevention, with sex-specific considerations as warranted. The data on sex-specific dose-response relationship between physical activity and stroke risk are inconclusive and warrant more research.

Integrity signals

Registry

Crossref · 10.1016/j.clinthera.2022.02.006

Cites

67 of 67 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

64 of 96 cited sources checked · 19 supported · 15 flagged · accuracy not yet measured

  • Findingcitation

    Five included studies specifically investigated occupational-related physical activity or commuting activity, either as the primary objective or in addition to leisure time activity.

    “five studies specifically investigated occupational-related physical activity or commuting activity,32,35,48,50,60 either as the primary objective or in addition to investigating leisure time activity.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [32] Blomstrand, 2014, Stroke incidence and association with risk factors in women: a 32-year follow-up of the Prospective Population Study of Women in Gothenburg, BMJ Open source

      The Methods (Potential risk factors for stroke; page not available) classify leisure-time physical activity, not occupational or commuting activity. Occupation is recorded only for socioeconomic status. This paper therefore does not fit the cited category of studies specifically investigating occupational or commuting activity. (LLM, conf=0.86)

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    • cites [35] Chomistek, 2013, Relationship of sedentary behavior and physical activity to incident cardiovascular disease: results from the Women's Health Initiative, J Am Coll Cardiol source

      The Methods (Exposure Assessment; page unavailable) specify that the physical-activity measure was leisure-time activity. The Discussion (page unavailable) says the study could not examine transportation separately because its questionnaire measured only total sitting time. Thus, this paper did not specifically investigate occupational or commuting physical activity as the citing sentence claims. (LLM, conf=0.88)

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    • cites [48] Mokhayeri, 2019, Effects of hypothetical interventions on ischemic stroke using parametric G-formula, Stroke source

      The Methods section describes an intervention involving intentional exercise of at least 210 minutes per week, so this paper does investigate physical activity. It does not identify that activity as occupational or commuting activity; the cited paper also cannot establish the citing review’s count of five studies. (LLM, conf=0.83)

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  • Findingcitation

    Among those 10 papers, 1 (10%) showed an effect of physical activity on ischemic stroke in men but not in women.

    “and 1 (10%)37 showed an effect in men but not women.37”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [37] Fan, 2019, Association between active commuting and incident cardiovascular diseases in Chinese: a prospective cohort study, J Am Hear Assoc source

      The Results (Subgroup Analyses; page unavailable) say the associations were generally similar across sex subgroups, with no significant interaction by sex. The Discussion likewise says the associations with major cardiovascular diseases were consistent among men and women, contrary to the attributed men-only effect on ischemic stroke. (LLM, conf=0.90)

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  • Findingown data

    Eight studies (29%) reported a non-significant association between physical activity and incident total stroke in women.

    “and eight (29%) reported a non-significant association between physical activity and incident total stroke.30,33,35,41,56,62,64,65”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [30] Autenrieth, 2013, Association between physical activity and risk of stroke subtypes: the atherosclerosis risk in communities study, Neuroepidemiology source
    • cites [33] Calling, 2006, Effects of body fatness and physical activity on cardiovascular risk: risk prediction using the bioelectrical impedance method, Scand J Public Heal source
    • cites [35] Chomistek, 2013, Relationship of sedentary behavior and physical activity to incident cardiovascular disease: results from the Women's Health Initiative, J Am Coll Cardiol source

      The Results section reports that decreased physical activity was associated with increased stroke risk in the women studied and says the associations remained statistically significant after further adjustment (Table 2). That contradicts describing this study as reporting a non-significant physical-activity–stroke association. The eight-study count and 29% are claims about the citing paper’s collection of studies, not findings this source can establish. (LLM, conf=0.87)

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  • Premisecitation

    The prior systematic review excluded papers that did not have at least three categories of physical activity because its focus was dose response.

    “Also, this prior systematic review21 excluded papers that did not have at least 3 categories of physical activity, as the focus was on dose response.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] Li, 2012, Physical activity and risk of cardiovascular disease—a meta-analysis of prospective cohort studies, Int J Env Res Public Heal. source
  • Interpretationcitation

    Known sex differences in associations between key metabolic factors and stroke make it biologically plausible that physical activity may be more strongly associated with stroke in women than in men.

    “there are well known sex differences in the associations between key metabolic factors and stroke that would make it biologically plausible that physical activity may be more strongly associated with stroke among women than men.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [8] Madsen, 2021, Sex and race differences in the risk of ischemic stroke associated with fasting blood glucose in REGARDS, Neurology source
    • cites [11] Peters, 2014, Diabetes as a risk factor for stroke in women compared with men: A systematic review and meta-analysis of 64 cohorts, including 775 385 individuals and 12 539 strokes, Lancet source
    • Rests on an assumption: There is a substantial lack of sex-stratified data on physical activity and stroke.
  • Classified as probably not a substantial claim. 23
  • May combine two claims. 25
  • The quote only partly states this claim. 2

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Of the 37 included studies, 31 were prospective cohort studies, 3 were case-control studies, and 3 were other study types.

    “Of the 37 studies included, 31 were prospective cohort studies with the exception of 3 case control studies,29,40,49 and 3 were other study types”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [29] Armstrong, 2015, Frequent physical activity may not reduce vascular disease risk as much as moderate activity: large prospective study of women in the United Kingdom, Circulation source

      The Statistical Analyses section describes an analysis of women in a single cohort, not a set of 37 included studies. Searches for the claimed counts and study types found no passage in our copy reporting 31 prospective cohorts, three case-control studies, and three other studies. No page number was available for the indexed passages. (LLM, conf=0.76)

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    • cites [40] Hu, 2001, Physical activity and risk for cardiovascular events in diabetic women, Ann Intern Med source
    • cites [49] Myint, 2009, Combined effect of health behaviours and risk of first ever stroke in 20,040 men and women over 11 years' follow-up in Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): prospective population study, Bmj source

      The citations in the sentence are attached to the three case-control studies, but this paper describes itself as a prospective population study (Methods; page not available). Its Case ascertainment section describes follow-up for incident strokes, not a case-control design. The paper does not establish the citing document’s overall count of 37 studies. (LLM, conf=0.87)

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  • May combine two claims.

    Findingown data

    Six papers reported testing a sex by physical activity interaction term for total stroke, and all showed non-significant interactions.

    “Six papers reported the testing of a sex by physical activity interaction term;33,38,40,41,50,52, all showing non-significant interactions.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [33] Calling, 2006, Effects of body fatness and physical activity on cardiovascular risk: risk prediction using the bioelectrical impedance method, Scand J Public Heal source
    • cites [38] Hall, 2019, Occupational and leisure-time physical activity differentially predict 6-year incidence of stroke and transient ischemic attack in women, Scand J Work Env Heal source

      The Methods (Study population; page not available) state that the analytic sample comprised 31,270 women, so this study could not test a sex-by-physical-activity interaction. The Methods (Statistical analyses; page not available) describe a possible time-by-covariate interaction, not a sex interaction, and report no non-significant sex-interaction result. (LLM, conf=0.90)

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    • cites [40] Hu, 2001, Physical activity and risk for cardiovascular events in diabetic women, Ann Intern Med source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    One of the 24 articles that included both sexes reported an effect estimate only for men because of the small sample size of women.

    “though one of these articles only reported an effect estimate for men due to the small sample size of women.38”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [38] Hall, 2019, Occupational and leisure-time physical activity differentially predict 6-year incidence of stroke and transient ischemic attack in women, Scand J Work Env Heal source

      The Methods (Study population; page not provided) state that the analytic sample comprised 31,270 women. The Discussion (Healthy worker effects; page not provided) likewise says only women employed at baseline were included. This paper therefore did not include both sexes or report a men-only effect estimate because of a small sample of women. (LLM, conf=0.90)

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    Findingown data

    Thirteen included papers included women only, and no included studies included only men.

    “Thirteen papers included women only,53–65 and no studies included only men.”
    Quote in the paperNot a substantial claim7 of 10 sources checked
    • cites [53] Qiao, 2012, Layperson-oriented vs. clinical-based models for prediction of incidence of ischemic stroke: National FINRISK Study, Int J Stroke source
    • cites [54] Sattelmair, 2010, Physical activity and risk of stroke in women, Stroke source
    • cites [55] Soares-Miranda, 2016, Physical activity and risk of coronary heart disease and stroke in older adults: the Cardiovascular Health Study, Circulation source

      The Methods > Population passage says the Cardiovascular Health Study enrolled men and women, so this cited paper was not a women-only study. The paper does not establish the sex composition of the citing document’s other included studies. (LLM, conf=0.88)

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    • cites [56] Tikk, 2014, Primary preventive potential for stroke by avoidance of major lifestyle risk factors: the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort, Stroke source

      Table 1 reports 11,062 men and 12,865 women in this study, and the Statistical Analysis section says analyses were performed separately for men and women. This paper therefore cannot be one of the women-only papers for which it is cited. It does not establish the citing review’s count of thirteen papers or whether that review included any men-only studies. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

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    • cites [57] Willey, 2009, Physical activity and risk of ischemic stroke in the Northern Manhattan Study, Neurology source

      The Results and Table 1 report that 62.8% of this paper’s cohort were women, so it included men and was not a women-only study. This paper cannot establish the citing document’s totals across all included studies, but it contradicts its apparent classification among the cited women-only papers. (LLM, conf=0.90)

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    • cites [58] Willey, 2017, Trajectories in leisure-time physical activity and risk of stroke in women in the California Teachers Study, Stroke source
    • cites [59] Williams, 2009, Reduction in incident stroke risk with vigorous physical activity: evidence from 7.7-year follow-up of the national runners' health study, Stroke source

      The Methods passage describes a cohort of 29,272 men and 12,123 women, so this cited paper is not a women-only study. This paper alone cannot establish whether any other studies included only men. (LLM, conf=0.91)

      Checked by a reasoning model — may be wrong.

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    • cites [60] Kurth, 2006, Healthy lifestyle and the risk of stroke in women, Arch Intern Med source
    • cites [61] Mora, 2007, Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms, Circulation source
    • cites [62] Aigner, 2017, Contribution of established stroke risk factors to the burden of stroke in young adults, Stroke source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Effect estimates in included studies were mostly relative measures such as hazard ratios or relative risks, though 3 papers reported absolute measures such as population attributable risk percents.

    “Effect estimates were mostly relative measures of the association between physical activity and incident stroke (either hazard ratios or relative risks), though 3 papers29,34,47 reported absolute measures of effect such as population attributable risk percents.”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [29] Armstrong, 2015, Frequent physical activity may not reduce vascular disease risk as much as moderate activity: large prospective study of women in the United Kingdom, Circulation source

      The Statistical Analyses section (page unavailable) says the paper reports hazard ratios, called relative risks, and the Results include incident stroke subtypes. It describes those ratios as ‘floated absolute risks’ for comparing categories, but our copy does not show population-attributable-risk percentages or another absolute measure of effect of the kind claimed. The count of three papers cannot be established from this source alone. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [34] Chomistek, 2018, Physical activity and incident cardiovascular disease in women: is the relation modified by level of global cardiovascular risk?, J Am Hear Assoc source

      The Methods (Statistical Analysis; page unavailable) say this study estimated hazard ratios for incident stroke, and the Results report those relative estimates. Our copy does not report a population-attributable-risk percentage or establish the citing paper’s count of three studies reporting absolute measures. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [47] McDonnell, 2013, Physical activity frequency and risk of incident stroke in a national US study of blacks and whites, Stroke source

      The Statistical analysis and Results sections report this study’s effect estimates as hazard ratios, not population-attributable risk percents. The population-attributable risk of 28.5% mentioned in the background is explicitly attributed to the separate INTERSTROKE study, so it is not an absolute effect estimate from this paper. (LLM, conf=0.87)

      Checked by a reasoning model — may be wrong.

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  • May combine two claims.

    Findingcitation

    Few papers (n=3) reported testing interaction terms or conducting a hypothesis test of a sex by physical activity interaction for ischemic stroke, and one demonstrated a significant sex interaction (P for interaction <0.05).

    “Few papers (n=3) reported that they tested interaction terms or conducted a hypothesis test of a sex by physical activity interaction,32,37,48 and one demonstrated a significant sex interaction (P for interaction <0.05).37”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [32] Blomstrand, 2014, Stroke incidence and association with risk factors in women: a 32-year follow-up of the Prospective Population Study of Women in Gothenburg, BMJ Open source

      The Methods (Statistical methods; page unavailable) describe a study of women and list the covariates in its Cox models; they include no sex-by-physical-activity interaction. The Results (Potential risk factors; page unavailable) report associations between inactivity and stroke outcomes, not a significant interaction between sexes. A women-only analysis cannot establish the attributed sex interaction. (LLM, conf=0.88)

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    • cites [37] Fan, 2019, Association between active commuting and incident cardiovascular diseases in Chinese: a prospective cohort study, J Am Hear Assoc source

      The Methods (Statistical Analysis) say the study tested interactions between commuting mode and sex using likelihood-ratio tests. But the Results (Subgroup Analyses) report no significant sex interaction; the only significant interaction identified was for marital status (P=0.033). Thus the testing claim is supported, but a significant sex interaction is not supported by this paper. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [48] Mokhayeri, 2019, Effects of hypothetical interventions on ischemic stroke using parametric G-formula, Stroke source

      The Discussion (page not available) reports an interaction test by sex, but it concerns the combined effect of six hypothetical interventions, not a sex-by-physical-activity interaction. Its reported interaction P value is 0.14, so the cited paper does not support the claim that it demonstrated a significant interaction (P<0.05). (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • The quote only partly states this claim.

    Findingcitation

    Seven studies (37%) demonstrated no evidence for reduced risk of incident ischemic stroke associated with physical activity in women.

    “and 7 (37%) demonstrated no evidence for reduced risk of incident stroke associated with physical activity.30,34,37,42,48,56,65”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites [30] Autenrieth, 2013, Association between physical activity and risk of stroke subtypes: the atherosclerosis risk in communities study, Neuroepidemiology source
    • cites [34] Chomistek, 2018, Physical activity and incident cardiovascular disease in women: is the relation modified by level of global cardiovascular risk?, J Am Hear Assoc source

      The Results report a significant association between greater physical activity and lower incident stroke risk in women (HR 0.72; 95% CI, 0.57–0.90). The Discussion likewise says physical activity was significantly inversely associated with incident stroke. The paper does not distinguish ischemic stroke in these passages, but its reported finding contradicts the citing sentence’s attribution of no evidence for reduced incident stroke risk. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

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    • cites [37] Fan, 2019, Association between active commuting and incident cardiovascular diseases in Chinese: a prospective cohort study, J Am Hear Assoc source

      The Results (Association Between Commuting Mode and CVDs; page unavailable) show no reduced ischemic-stroke risk for walking, which supports a narrower null finding. But they report an inverse association for cycling, and the Discussion says the associations were consistent among men and women. The source therefore does not support describing its ischemic-stroke findings in women as wholly showing no evidence of reduced risk. The seven-study count is the citing paper’s synthesis, not a finding attributed to this individual study. (LLM, conf=0.82)

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    One study did not report the effect estimate for women because of small case numbers and was not included in Table 2.

    “One study38 did not report the effect estimate for women due to small case numbers; and this study was not included in Table 2.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [38] Hall, 2019, Occupational and leisure-time physical activity differentially predict 6-year incidence of stroke and transient ischemic attack in women, Scand J Work Env Heal source

      The Methods (Study population; page unavailable) say the analytic sample comprised 31,270 women. The Results (page unavailable) explicitly report effect estimates for women and state that the paper’s Table 2 displays hazard ratios for stroke. This contradicts the attributed reason that the study did not report women’s effect estimates because of small case numbers; the citing document’s decision to omit it from its own Table 2 cannot be verified from this source. (LLM, conf=0.90)

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Several mechanisms have been suggested for favorable effects of physical activity, including improvement in hypertension, diabetes, body weight, atherosclerotic processes, endothelial dysfunction, cerebral blood flow, platelet aggregability, and insulin sensitivity.

    “Various mechanisms are suggested for favorable effects of physical activity, some of which are mediated by improving other known risk factors of cardiovascular disease such as hypertension, diabetes, and body weight. Additionally, physical activity could potentially slow the atherosclerotic process and endothelial dysfunction, improve cerebral blood flow (CBF),15,16 decrease platelets’ aggregabil”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [15] Kastrup, 1997, Sex dependency of cerebrovascular CO2 reactivity in normal subjects, Stroke source
    • cites [16] Murrell, 2013, Cerebral blood flow and cerebrovascular reactivity at rest and during sub-maximal exercise: Effect of age and 12-week exercise training, Age (Omaha) source
    • cites [17] Gambardella, 2020, Pathophysiological mechanisms underlying the beneficial effects of physical activity in hypertension, J Clin Hypertens source

      The sections on endothelial function and insulin sensitivity describe exercise-related improvements, and the paper states that physical activity lowers blood pressure. The angiogenesis section discusses increased blood-flow reserves, but does not identify cerebral blood flow; the copy also does not substantiate the claimed effects on platelet aggregability or body weight. No page numbers are available in the indexed copy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other data showed favorable effects of physical activity on stroke in both sexes.

    “Other data showed favorable effects in both sexes;20”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [20] Shinton, 1993, Lifelong exercise and stroke, Br Med J. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Women in North America carry a larger stroke burden than men, including higher lifetime stroke risk, higher lifetime stroke death risk, and worse post-stroke outcomes.

    “In North America, women bear a greater burden of disease due to a higher lifetime risk of stroke,1 a higher lifetime risk of death from stroke, and a higher risk of poor outcomes following stroke compared with men.2–4”
    Quote in the paperNot a substantial claim4 of 4 sources checked
    • cites [1] 2018, Global, regional, and country-specific lifetime risks of stroke, 1990 and 2016, N Engl J Med source
    • cites [2] Reeves, 2008, Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes, Lancet Neurol. source

      The Mortality section reports more total stroke deaths among women in the USA, and Functional outcomes and quality of life reports consistently poorer post-stroke outcomes for women, including in North American studies. The paper does not establish a higher lifetime risk of dying from stroke; it reports lower age-adjusted stroke mortality rates for women and substantial variation by age. The sentence cites a different source for lifetime stroke risk. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [3] Lisabeth, 2015, Factors influencing sex differences in poststroke functional outcome, Stroke source

      The Results and Discussion report worse 90-day functional outcomes for women after stroke. They do not establish a higher lifetime risk of stroke or death from stroke; the Results instead report no sex difference in age-adjusted 90-day mortality. The Discussion also cautions that findings from one south Texas community may not generalize across North America. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [4] Virani, 2021, Heart disease and stroke statistics—2021 update: a report from the American Heart Association, Circulation source

      The Summary’s Stroke section (Chapter 15; page unavailable) reports US stroke-mortality trends by age, but does not compare women with men. Searches for lifetime stroke risk, lifetime risk of stroke death, and post-stroke outcomes found no passage in our copy establishing the claimed sex differences. (LLM, conf=0.70)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Other prior reviews investigated only specific types of physical activity, included only women, or did not report stroke outcomes separately.

    “Other prior reviews have only investigated specific types of physical activity,22,23 include only women,24,25 or don’t report stroke outcomes separately.26”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [22] Boone-Heinonen, 2009, Walking for prevention of cardiovascular disease in men and women: a systematic review of observational studies, Obes Rev source
    • cites [23] Hamer, 2008, Active commuting and cardiovascular risk: a meta-analytic review, Prev Med source
    • cites [24] Oguma, 2004, Physical activity decreases cardiovascular disease risk in women: review and meta-analysis, Am J Prev Med source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The American Heart Association recommends moderate to vigorous aerobic physical activity for at least 40 minutes per day, 3 to 4 days per week, to prevent stroke.

    “The American Heart Association (AHA) recommends moderate to vigorous aerobic physical activity at least 40 min a day, 3 to 4 days per week, to prevent stroke.12,13”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [12] Meschia, 2014, Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association, Stroke source
    • cites [13] Bushnell, 2014, Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association, Stroke source

      The “Obesity, Metabolic Syndrome, and Lifestyle Factors: Recommendations” section recommends regular physical activity for primary stroke prevention in women with cardiovascular risk factors and diet-and-exercise interventions for people at high risk. It does not specify moderate-to-vigorous aerobic activity, 40 minutes a day, or 3 to 4 days per week. No page number is available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    A prior systematic review that included stroke as a secondary outcome reported only data through 2010, treated sex-specific estimates as exploratory, and did not report ischemic stroke separately.

    “In a past systematic review that included stroke as a secondary outcome,21 only data through 2010 were reported, reporting sex-specific estimates was an exploratory objective, and data on ischemic strokes was not reported separately.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] Li, 2012, Physical activity and risk of cardiovascular disease—a meta-analysis of prospective cohort studies, Int J Env Res Public Heal. source

      Methods §2.1 limits the literature search to December 2010, the Introduction says sex-specific associations were explored where possible, and the Discussion says ischemic and hemorrhagic stroke were not analyzed separately. The paper includes stroke as an outcome, but describes it and coronary heart disease as two major types of cardiovascular disease rather than designating stroke a secondary outcome. Page numbers are unavailable in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Physical activity is a known protective factor for mortality and cardiovascular disease.

    “Physical activity, a known protective risk factor for mortality and cardiovascular disease,10”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [10] Yusuf, 2020, Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study, Lancet source

  • May combine two claims.

    Findingcitation

    One of the 17 papers demonstrated a higher population attributable risk of total stroke due to physical inactivity in women than men (63.8% vs 57.6%), but the difference was not tested for statistical significance.

    “One paper29 (of the 17) demonstrated a higher population attributable risk of stroke due to physical inactivity in women than men (63.8% vs. 57.6%), but the difference was not tested for statistical significance.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [29] Armstrong, 2015, Frequent physical activity may not reduce vascular disease risk as much as moderate activity: large prospective study of women in the United Kingdom, Circulation source

      The Results and Table 3 report stroke associations with physical activity in women, but give no population-attributable-risk estimates for women and men. A search for 63.8%, 57.6%, and sex-specific population attributable risk found no matching passage in our copy; the Statistical Analyses section describes tests across stroke subtypes, not between sexes. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Because inadequate physical activity is linked to diabetes and metabolic syndrome, and diabetes and fasting blood glucose have a stronger association with incident stroke in women than men, lack of physical activity may be a stronger predictor of stroke in women than men.

    “given that inadequate physical activity is linked to the development of diabetes and metabolic syndrome, and the association between diabetes and fasting blood glucose and incident stroke is stronger in women than men,8,11 lack of physical activity may also be a stronger predictor of stroke in women than men.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [8] Madsen, 2021, Sex and race differences in the risk of ischemic stroke associated with fasting blood glucose in REGARDS, Neurology source

      Split into 3 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [11] Peters, 2014, Diabetes as a risk factor for stroke in women compared with men: A systematic review and meta-analysis of 64 cohorts, including 775 385 individuals and 12 539 strokes, Lancet source
    • Rests on an assumption: There is a substantial lack of sex-stratified data on physical activity and stroke.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The AHA guideline for preventing stroke in women identified physical inactivity as a risk factor with similar prevalence in men and women but with an unknown difference in effect by sex.

    “The AHA guideline for preventing stroke in women identified physical inactivity as a risk factor with similar prevalence in men and women but with an unknown difference in effect by sex.13”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [13] Bushnell, 2014, Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association, Stroke source

      The “Lifestyle” and “Obesity, Abdominal Adiposity, and Metabolic Syndrome: Summary and Gaps” sections associate physical activity with lower stroke risk and say little is known about sex differences in the effects of healthy lifestyle. The passages do not establish that physical inactivity has similar prevalence in men and women; searches for physical inactivity and its prevalence did not find that comparison. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The search strategy was adapted from a published PubMed search tool previously validated to identify papers on biologic sex or gender differences in disease states.

    “Our initial search strategy was an adaptation of a published PubMed search tool which has been previously validated to identify papers designed to identify either biologic sex or gender differences in particular disease states.27”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Song, 2016, Development of a PubMed based search tool for identifying sex and gender specific health literature, J Women's Heal source

  • The quote only partly states this claim.

    Findingown data

    Of the 28 studies in Table 2, 19 (68%) reported estimates indicating a protective effect of physical activity on risk of total stroke in women.

    “Of the 28 studies in Table 2, Nineteen studies (68%) reported estimates indicating a protective effect of physical activity on risk of stroke”
    • Also stated in: § Findings: · boosted
      “For women specifically, the majority of included studies demonstrated a reduced risk of incident stroke with physical activity”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [29] Armstrong, 2015, Frequent physical activity may not reduce vascular disease risk as much as moderate activity: large prospective study of women in the United Kingdom, Circulation source

      The Discussion (page unavailable in our copy) reports lower stroke risk among more active women, consistent with the claim’s general direction. But this paper reports a prospective study of UK women, not a tally of 28 studies; our copy does not substantiate the asserted 19 studies (68%) or their placement in Table 2. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [31] Barengo, 2017, Leisure-time physical activity reduces total and cardiovascular mortality and cardiovascular disease incidence in older adults, J Am Geriatr Soc source
    • cites [36] Cuthbertson, 2019, Associations of leisure-time physical activity and television viewing with life expectancy free of nonfatal cardiovascular disease: the ARIC study, J Am Hear Assoc source

      The Results (Table 2; page unavailable) associate higher leisure-time physical activity with lower risk of nonfatal stroke in the ARIC cohort. But this is one cohort study, not a review of 28 studies; it does not report that 19 studies (68%) found a protective effect, nor does Table 2 give that count for women. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • Rests on an assumption: The sex-specific effect estimates reported by the included studies are valid and comparable enough to support a narrative synthesis of sex differences.

  • May combine two claims.

    Study design and conductcitation

    Self-report of physical activity may be affected by recall or reporting bias, but self-report is still a valid method, especially in observational and population-based studies.

    “Though self-report may be affected by recall or reporting bias, self-report of physical activity is still a valid method, especially in observational and population-based studies.66”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [66] Sattler, 2021, Physical activity self-reports: past or future?, Br J Sports Med source

  • May combine two claims.

    Findingown data

    All included studies obtained physical activity data using participant self-report, and none used objectively measured physical activity.

    “All studies obtained data on physical activity using participant self-report (e.g., questionnaires); none of the studies used objectively measured physical activity (i.e., measurement using devices).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Of the 37 included articles, 24 included both women and men.

    “Of the 37 articles, 24 included both women and men in the study,29–52”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 29–52

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Twenty-nine included papers reported estimates for all strokes, and 19 included effect estimates for ischemic strokes specifically.

    “Twenty-nine papers included estimates for all strokes (ischemic and hemorrhagic), and 19 papers included effect estimates for ischemic strokes specifically.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Excluding studies that measured only occupational physical activity, commuting, or only absolute effect, the relative risk reduction for stroke in women varied from 11% to 51% for total stroke and from 11% to 72% for ischemic stroke.

    “Excluding those studies that measured only occupational-physical activity, commuting, or those that only reported an absolute measure of effect, the relative risk reduction for stroke was apparent, but widely varied across studies and level of physical activity from 11% to 51% for total stroke and from 11% to 72% for ischemic stroke.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Data on race and ethnicity of participants in some included studies was not complete.

    “Finally, data on race and ethnicity of participants in some of the studies was not complete”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Models in included studies were commonly adjusted for age, demographic factors, comorbidities, BMI, and other lifestyle factors.

    “Models were commonly adjusted for age, demographic, comorbidities, BMI and other lifestyle factors (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Studies were conflicted about whether the association between physical activity and incident stroke differed by sex, with 35% of total stroke studies showing a significant association in women but not men and fewer showing a stronger association in men than women.

    “Studies were conflicted as to whether the association between physical activity and incident stroke differed by sex, with 35% of the studies on total stroke demonstrating a significant association in women but not in men and fewer demonstrating a stronger association in men than women.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Some included studies reported reduced stroke risk with leisure time physical activity but no reduced stroke risk associated with increased occupational activity or commuting.

    “Some studies reported differing effects between leisure time physical activity and occupational50 or commuting activity and reported reduced stroke risk with leisure time physical activity but no reduced stroke risk associated with increased occupational activity or commuting.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Myint, 2006, Combined work and leisure physical activity and risk of stroke in men and women in the European prospective investigation into Cancer-Norfolk Prospective Population Study, Neuroepidemiology source

  • May combine two claims.

    Findingown data

    In women, the majority of included studies demonstrated a reduced risk of incident stroke associated with physical activity, with relative risk reductions ranging from 11% to 72%, though most estimates fell between 20% and 40%.

    “For women specifically, the majority of included studies demonstrated a reduced risk of incident stroke with physical activity with relative risk reductions ranging from 11% to 72%, though most estimates fell between 20% and 40%.”
    • Also stated in: § DISCUSSION · plain
      “we found that among women, the majority of the studies demonstrated a reduced risk of incident stroke associated with physical activity with estimates ranging from 11% to 72%, though most estimates fell in the 20% to 40% range.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The sex-specific effect estimates reported by the included studies are valid and comparable enough to support a narrative synthesis of sex differences.

  • Classified as probably not a substantial claim.

    Premisecitation

    The Framingham study indicated that moderate or intense physical activity is protective against stroke in men but not in women.

    “The Framingham study indicated that moderate or intense physical activity is protective against stroke in men but not in women.19”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Kiely, 1994, Physical activity and stroke risk: the Framingham Study, Am J Epidemiol. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Titles and abstracts were screened by study authors, and each full-text manuscript was evaluated by two study authors.

    “titles and abstracts were first screened for possible inclusion by study authors. Following screening of titles and abstracts, each full text manuscript was evaluated by two study authors”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The review did not pool data because it was not designed as a meta-analysis.

    “We did not attempt to pool data as this was not designed as a meta-analysis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The review used a pre-specified search strategy.

    “Using a pre-specified search strategy, we searched PubMed/MEDLINE and Cochrane Central”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Inclusion criteria for the review were determined a priori by the study authors.

    “Criteria for inclusion for the study were determined a priori by study authors”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The review did not separately investigate hemorrhagic strokes.

    “We did not separately investigate hemorrhagic strokes in our analysis”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The wide heterogeneity of physical activity categorization, differing study populations, and potentially differing covariates may contribute to conflicting results between studies.

    “The wide degree of heterogeneity of how physical activity was categorized, along with differing study populations and potentially differing covariates in the models, may contribute to conflicting results between studies”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    The review did not pool effect estimates or perform a meta-analysis.

    “In addition, we did not pool effect estimates or perform a meta-analysis.”
    Quote in the paperSubstantial claim
38 of 38

  • The paper relies on this without support.

    The AHA recommendation for physical activity to prevent stroke is mainly based on observational studies and lacks strong clinical trials.

    “This recommendation is mainly based on observational studies, and the lack of strong clinical trials leads to many knowledge gaps.”

  • The paper relies on this without support.

    There is a substantial lack of sex-stratified data on physical activity and stroke.

    “there is still a substantial lack of sex-stratified data for physical activity and stroke”

  • The paper relies on this without support.

    The sex-specific effect estimates reported by the included studies are valid and comparable enough to support a narrative synthesis of sex differences.

    “We did not attempt to pool data as this was not designed as a meta-analysis.”
    “There was substantial heterogeneity in the constructs used to measure physical activity (Table 1).”
3 of 3

Cites

Flagged first, then by citations

5 of the 72 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Covidence Systematic Review Software, Veritas Health Innovation, Melbourne, Australia. Available at www.covidence.org.

Cited by

Sorted by citations

Related

Authors
Madsen, T. E., Samaei, M., Pikula, A., Yu, A. Y. X., Carcel, C., Millsaps, E., Yalamanchili, R. S., Bencie, N., Dula, A. N., Leppert, M., Rundek, T., Dreyer, R. P., & Bushnell, C.
Affiliations
  • Brown University (US)
  • University Health Network (CA)
  • Sunnybrook Health Science Centre (CA)
  • UNSW Sydney (AU)
  • Reid Health (US)
  • Pacific Northwest University of Health Sciences (US)
  • The University of Texas at Austin (US)
  • University of Colorado Anschutz (US)
  • University of Miami (US)
  • Yale University (US)
  • Wake Forest University Health Sciences (US)
ORCID
Venue
Clinical Therapeutics
Publisher
Elsevier BV
Published
2022-04
Volume
44
Issue
4
Pages
586-611
ISSN
0149-2918 (ISSN-L)
DOI
10.1016/j.clinthera.2022.02.006
PMC
PMC9195871
OpenAlex
W4223641903
Cited by
27
References
72
Citations by year
2026: 4 · 2025: 9 · 2024: 11 · 2023: 2 · 2022: 1
FWCI
0.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Heart Association (847469)
  • National Institutes of Health (UL1TR001420, KL2TR002737, KL2TR002534, UL1TR002736)
  • Agency for Healthcare Research and Quality (R01 HS025723)
  • National Heart, Lung, and Blood Institute (K23HL140081, L30 HL143706)
  • National Institute of Neurological Disorders and Stroke (R01NS040807, R01NS029993, U24NS107235, U24NS107267)
  • National Center for Advancing Translational Sciences
  • National Institute on Minority Health and Health Disparities (R01MD012467)
Topics
  • Health Sciences › Medicine › Physiology › Physical Activity and Health
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
Keywords
physical activity, sex differences, stroke, ischemic stroke, hemorrhagic stroke, primary stroke prevention, women, cardiovascular risk factors, physical inactivity
MeSH terms
Ischemic Stroke, Female, Humans, Male, Risk Factors, Sex Characteristics, Exercise, Stroke

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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