Effects of hypothetical interventions on ischemic stroke using parametric G-formula
Abstract
Background and Purpose—: Standard analytic approaches (eg, logistic regression) fail to adequately control for time-dependent confounding and, therefore, may yield biased estimates of the total effect of the exposure on the outcome. In the present study, we estimate the effect of body mass index, intentional physical activity, HDL (high-density lipoprotein) cholesterol, LDL (low-density lipoprotein) cholesterol, hypertension, and cigarette smoking on the 11-year risk of ischemic stroke by sex using the parametric g-formula to control time-dependent confounders. Methods—: Using data from the MESA (Multi-Ethnic Study of Atherosclerosis), we followed 6809 men and women aged 45 to 84 years. We estimated the risk of stroke under 6 hypothetical interventions: maintaining body mass index <25 kg/m 2 , maintaining normotension (systolic blood pressure <140 and diastolic <90 mm Hg), quitting smoking, maintaining HDL >1.55 mmol/L, maintaining LDL <3.11 mmol/L, and exercising at least 210 minutes per week. The effects of joint hypothetical interventions were also simulated. Results—: In men, the 11-year risk of ischemic stroke would be reduced by 85% (95% CI, 66–96) for all 6 hypothetical interventions. In women, this same effect was estimated as 55% (95% CI, 6–82). Conclusions—: The hypothetical interventions explored in our study resulted in risk reduction in both men and women.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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.”
From Sex Differences in Physical Activity and Incident Stroke: A Systematic Review (2022) · cites this paper as [48]
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)
Experimental — accuracy not yet measuredFew 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”
From Sex Differences in Physical Activity and Incident Stroke: A Systematic Review (2022) · cites this paper as [48]
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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Lichtenstein, A. H., Appel, L. J., Brands, M., Carnethon, M., Daniels, S., Franch, H. A., Franklin, B., Kris-Etherton, P., Harris, W. S., Howard, B., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.176158 · Cited by 2,705 · see citing works
O'Donnell, M. J., Chin, S. L., Rangarajan, S., Xavier, D., Liu, L., Zhang, H., Rao-Melacini, P., Zhang, X., Pais, P., Agapay, S., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30506-2 · Cited by 2,296 · see citing works
Cerebrovascular disease in the community: results of a WHO collaborative study.
Aho, K., Harmsen, P., Hatano, S., Marquardsen, J., Smirnov, V. E., & Strasser, T. (1980) · Europe PMC (PubMed Central) · Cited by 1,284 · see citing works
Sparse data bias: a problem hiding in plain sight
Greenland, S., Mansournia, M. A., & Altman, D. G. (2016) · BMJ · doi:10.1136/bmj.i1981 · Cited by 898 · cited 1× · see citing works
“We acknowledge the possibility of sparse data bias and low precision of effect estimates (represented by wide confidence intervals).(14) We did not adjust for dietary pattern because for 577 participants there was no measurement of the dietary pattern, which challenges the assumption of no unmeasured confounders.”
BackgroundSelf-citationPopulation attributable fraction
Mansournia, M. A., & Altman, D. G. (2018) · BMJ · doi:10.1136/bmj.k757 · Cited by 478 · see citing works
Self-citationMansournia, M. A., & Altman, D. G. (2016) · BMJ · doi:10.1136/bmj.i189 · Cited by 434 · see citing works
Self-citationIntervening on risk factors for coronary heart disease: an application of the parametric g-formula.
Taubman, S., Robins, J., Mittleman, M., & Hernán, M. (2009) · International Journal of Epidemiology · doi:10.1093/ije/dyp192 · Cited by 359 · see citing works
Handling time varying confounding in observational research
Mansournia, M. A., Etminan, M., Danaei, G., Kaufman, J. S., & Collins, P. G. S. (2017) · BMJ · doi:10.1136/bmj.j4587 · Cited by 343 · see citing works
Self-citationMatched designs and causal diagrams
Mansournia, M. A., Hernán, M. Á., & Greenland, S. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dyt083 · Cited by 161 · see citing works
Self-citationPhysical activity and risk of ischemic stroke in the Northern Manhattan Study
Willey, J. Z., Moon, Y. P., Paik, M. C., Boden-Albala, B., Sacco, R. L., & Elkind, M. S. V. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c34b58 · Cited by 122 · see citing works
PHYSICAL ACTIVITY AND RISK OF ISCHEMIC STROKE IN THE NORTHERN MANHATTAN STUDY
Landau, W. M. (2010) · Neurology · doi:10.1212/wnl.0b013e3181e03150 · Cited by 110 · see citing works
Tikk, K., Sookthai, D., Monni, S., Gross, M.-L., Lichy, C., Kloss, M., & Kaaks, R. (2014) · Stroke · doi:10.1161/strokeaha.114.005025 · Cited by 64 · see citing works
Shakiba, M., Mansournia, M. A., Salari, A., Soori, H., Mansournia, N., & Kaufman, J. S. (2017) · American Journal of Epidemiology · doi:10.1093/aje/kwx360 · Cited by 36 · see citing works
Self-citationMansournia, M. A., Naimi, A. I., & Greenland, S. (2018) · American Journal of Epidemiology · doi:10.1093/aje/kwy273 · Cited by 36 · see citing works
Self-citationVangen-Lønne, A. M., Ueda, P., Gulayin, P., Wilsgaard, T., Mathiesen, E. B., & Danaei, G. (2018) · European Journal of Epidemiology · doi:10.1007/s10654-017-0344-x · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Sex Differences in Physical Activity and Incident Stroke: A Systematic Review
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., et al. (2022) · Clinical Therapeutics · doi:10.1016/j.clinthera.2022.02.006 · Cited by 27 · see citing works
- Authors
- Mokhayeri, Y., Hashemi-Nazari, S. S., Khodakarim, S., Safiri, S., Mansournia, N., Mansournia, M. A., Kaufman, J. S., & Naimi, A. I.
- Affiliations
- Lorestan University of Medical Sciences (IR)
- Department of Epidemiology, Safety Promotion and Injury Prevention Research Center (S.S.H.-N.), Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Shahid Beheshti University (IR)
- Tabriz University of Medical Sciences (IR)
- Aja University of Medical Sciences (IR)
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran (M.A.M.)
- McGill University (CA)
- University of Pittsburgh (US)
- ORCID
- Venue
- Stroke
- Published
- 2019-11
- Volume
- 50
- Issue
- 11
- Pages
- 3286-3288
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- OpenAlex
- W2971852555
- Semantic Scholar
- bb301080142532731eed95a770bc85a2fcb0031a
- Cited by
- 32
- References
- 15
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 5
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- Topics
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Keywords
- ischemic stroke, parametric g-formula, time-varying confounding, hypothetical interventions, body mass index, physical activity, HDL cholesterol, LDL cholesterol, hypertension, smoking cessation, sex differences, stroke risk reduction, Multi-Ethnic Study of Atherosclerosis
- MeSH terms
- Aged, Aged, 80 and over, Brain Ischemia, Female, Humans, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Models, Cardiovascular, Risk Factors, Sex Factors, Exercise, Body Mass Index, 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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
