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Title [sv]
Varför är vården och hälsan ojämlik? Identifiering av mekanismer bakom socioekonomiska skillnader i strokevård och utfall med hjälp av innovativa statistiska metoder för mediationanalys.
Title [en]
Uncovering the mechanisms behind socioeconomic inequalities in stroke care and outcome through innovative statistical methods for mediation analysis
Abstract [en]
Stroke is a leading cause of death and disability in the western world. In Sweden, research has shown that socially underprivileged patients have poorer access to stroke care at the acute stage as well as secondary prevention after their stroke and are more prone to adverse outcome. That these differences exist is well established but the question remains why, and how they can be prevented.With this interdisciplinary project we seek to answer these questions. The project is a collaboration with Riksstroke, the Swedish stroke register, and will have access to unique linked register data. By combining these high quality data with the implementation and development of advanced statistical methods related to the emerging field of causal mediation analysis we will be able to give novel insights into the causal mechanisms behind social inequalities in health. We aim toinvestigate the causal pathways behind socioeconomic inequalities in stroke care and outcomeevaluate and implement recent developments in mediation analysis for complex causal pathways in the stroke contextdevelop flexible techniques for sensitivity analysis to evaluate the impact of violations of the assumptions behind mediation analysis, for more reliable estimates of causal pathwaysimplement the developed methods in publically available softwareUsing the stroke example we will thus provide means to solve the key question of underlying causes of socioeconomic differences in health.
Publications (6 of 6) Show all publications
Lindmark, A. & Darehed, D. (2025). Investigating multiple mediators to mitigate socioeconomic differences in patient‐reported outcomes after stroke: a nationwide register‐based study. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 14(5), Article ID e039466.
Open this publication in new window or tab >>Investigating multiple mediators to mitigate socioeconomic differences in patient‐reported outcomes after stroke: a nationwide register‐based study
2025 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, E-ISSN 2047-9980, Vol. 14, no 5, article id e039466Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Substantial socioeconomic differences in patient-reported outcome measures (PROMs) 3 months after stroke have recently been shown. We aimed to understand the underlying mechanisms and investigate potential interventional targets to equalize differences.

METHODS: All patients aged 18 to 64 years, independent in activities of daily living, registered with a first-time stroke in Riksstroke (the Swedish Stroke Register) from 2015 to 2017 were included. PROMs 3 months after stroke included activities of daily living status, mood, fatigue, pain, and general health. Socioeconomic status (SES) was measured on the basis of income and education. Using causal mediation analysis, we simulated the effect of interventions on the distributions of smoking, metabolic health (diabetes, antihypertensive treatment, statin treatment), atrial fibrillation, and stroke characteristics (stroke type, severity) on the absolute SES-related risk difference in PROMs.

RESULTS: Of 6910 patients, 8% had become dependent in activities of daily living, 13% reported low mood, 42% fatigue, 23% pain, and 17% poor general health 3 months after stroke. Adjusted for sex and age, low SES was associated with increased absolute risks of poor PROMs with between 6% and 18% compared with higher SES with the largest increase for general health (18.2% [95% CI, 13.5%-22.9%]). Intervening to shift the distribution of all mediators among patients with low SES to those of patients with higher SES potentially reduces SES disparities by a proportion of 14% to 45%. For most PROMs the most important intervention was reducing smoking and improving metabolic health.

CONCLUSIONS: Working-age patients with low SES report more severe outcomes 3 months after stroke than patients with higher SES. Targeted interventions reducing the prevalence of smoking, diabetes, hypertension, and high cholesterol in patients with low SES could mitigate these disparities.

Place, publisher, year, edition, pages
American Heart Association, 2025
Keywords
low socioeconomic status, mediation analysis, patient‐reported outcome measures, risk factors, stroke
National Category
Public Health, Global Health and Social Medicine Cardiology and Cardiovascular Disease
Identifiers
urn:nbn:se:umu:diva-235619 (URN)10.1161/jaha.124.039466 (DOI)001436103200001 ()39968803 (PubMedID)2-s2.0-86000545732 (Scopus ID)
Funder
Swedish Research Council, 2018-02670
Available from: 2025-02-20 Created: 2025-02-20 Last updated: 2025-04-15Bibliographically approved
Lindmark, A., von Euler, M., Glader, E.-L., Sunnerhagen, K. S. & Eriksson, M. (2024). Socioeconomic differences in patient reported outcome measures 3 months after stroke: a nationwide Swedish register-based study. Stroke, 55(8), 2055-2065
Open this publication in new window or tab >>Socioeconomic differences in patient reported outcome measures 3 months after stroke: a nationwide Swedish register-based study
Show others...
2024 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 55, no 8, p. 2055-2065Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: There is a well-known association between low socioeconomic status (SES), poor survival, and clinician-reported outcomes after stroke. We aimed to assess socioeconomic differences in Patient Reported Outcome Measures 3 months after stroke.

METHODS: This nationwide cohort study included patients registered with acute stroke in the Swedish Stroke Register 2015-2017. Patient Reported Outcome Measures included activities of daily living (mobility, toileting, and dressing), and poststroke symptoms (low mood, fatigue, pain, and poor general health). Information on SES prestroke was retrieved from Statistics Sweden and defined by a composite measure based on education and income tertiles. Associations between SES and Patient Reported Outcome Measures were analyzed using logistic regression adjusting for confounders (sex and age) and additionally for potential mediators (stroke type, severity, cardiovascular disease risk factors, and living alone). Subgroup analyses were performed for stroke type, men and women, and younger and older patients.

RESULTS: The study included 44 511 patients. Of these, 31.1% required assistance with mobility, 18% with toileting, and 22.2% with dressing 3 months after stroke. For poststroke symptoms, 12.3% reported low mood, 39.1% fatigue, and 22.7% pain often/constantly, while 21.4% rated their general health as poor/very poor. Adjusted for confounders, the odds of needing assistance with activities of daily living were highest for patients with low income and primary school education, for example, for mobility, odds ratio was 2.06 (95% CI, 1.89-2.24) compared with patients with high income and university education. For poststroke symptoms, odds of poor outcome were highest for patients with low income and university education (eg, odds ratio, 1.79 [95% CI, 1.49-2.15] for low mood). Adjustments for potential mediators attenuated but did not remove associations. The associations were similar in ischemic and hemorrhagic strokes and more pronounced in men and patients <65 years old.

CONCLUSIONS: There are substantial SES-related differences in Patient Reported Outcome Measures poststroke. The more severe outcome associated with low SES is more pronounced in men and in patients of working age.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2024
Keywords
Patient Reported Outcome Measures, activities of daily living, health status, low socioeconomic status, stroke
National Category
Public Health, Global Health and Social Medicine Neurology
Identifiers
urn:nbn:se:umu:diva-227614 (URN)10.1161/STROKEAHA.124.047172 (DOI)001272487000011 ()38946533 (PubMedID)2-s2.0-85199283597 (Scopus ID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2018-00852Swedish Research Council, 2018-02670
Available from: 2024-07-01 Created: 2024-07-01 Last updated: 2025-04-24Bibliographically approved
Lindmark, A. (2022). Sensitivity analysis for unobserved confounding in causal mediation analysis allowing for effect modification, censoring and truncation. Statistical Methods & Applications, 31, 785-814
Open this publication in new window or tab >>Sensitivity analysis for unobserved confounding in causal mediation analysis allowing for effect modification, censoring and truncation
2022 (English)In: Statistical Methods & Applications, ISSN 1618-2510, E-ISSN 1613-981X, Vol. 31, p. 785-814Article in journal (Refereed) Published
Abstract [en]

Causal mediation analysis is used to decompose the total effect of an exposure on an outcome into an indirect effect, taking the path through an intermediate variable, and a direct effect. To estimate these effects, strong assumptions are made about unconfoundedness of the relationships between the exposure, mediator and outcome. These assumptions are difficult to verify in a given situation and therefore a mediation analysis should be complemented with a sensitivity analysis to assess the possible impact of violations. In this paper we present a method for sensitivity analysis to not only unobserved mediator-outcome confounding, which has largely been the focus of previous literature, but also unobserved confounding involving the exposure. The setting is estimation of natural direct and indirect effects based on parametric regression models. We present results for combinations of binary and continuous mediators and outcomes and extend the sensitivity analysis for mediator-outcome confounding to cases where the continuous outcome variable is censored or truncated. The proposed methods perform well also in the presence of interactions between the exposure, mediator and observed confounders, allowing for modeling flexibility as well as exploration of effect modification. The performance of the method is illustrated through simulations and an empirical example. 

Place, publisher, year, edition, pages
Springer, 2022
Keywords
Statistics, Probability and Uncertainty, Statistics and Probability
National Category
Probability Theory and Statistics
Research subject
Statistics
Identifiers
urn:nbn:se:umu:diva-190068 (URN)10.1007/s10260-021-00611-4 (DOI)000725907700001 ()2-s2.0-85120563176 (Scopus ID)
Funder
Swedish Research Council, 2018-02670Forte, Swedish Research Council for Health, Working Life and Welfare, 2018-00852
Available from: 2021-12-03 Created: 2021-12-03 Last updated: 2022-12-06Bibliographically approved
Lindmark, A., Eriksson, M. & Darehed, D. (2022). Socioeconomic status and stroke severity: Understanding indirect effects via risk factors and stroke prevention using innovative statistical methods for mediation analysis. PLOS ONE, 17(6), Article ID e0270533.
Open this publication in new window or tab >>Socioeconomic status and stroke severity: Understanding indirect effects via risk factors and stroke prevention using innovative statistical methods for mediation analysis
2022 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 6, article id e0270533Article in journal (Refereed) Published
Abstract [en]

Background: Those with low socioeconomic status have an increased risk of stroke, more severe strokes, reduced access to treatment, and more adverse outcomes after stroke. The question is why these differences are present. In this study we investigate to which extent the association between low socioeconomic status and stroke severity can be explained by differences in risk factors and stroke prevention drugs.

Methods: The study included 86 316 patients registered with an ischemic stroke in the Swedish Stroke Register (Riksstroke) 2012–2016. Data on socioeconomic status was retrieved from the Longitudinal integrated database for health insurance and labour market studies (LISA) by individual linkage. We used education level as proxy for socioeconomic status, with primary school education classified as low education. Stroke severity was measured using the Reaction Level Scale, with values above 1 classified as severe strokes. To investigate the pathways via risk factors and stroke prevention drugs we performed a mediation analysis estimating indirect and direct effects.

Results: Low education was associated with an excess risk of a severe stroke compared to mid/high education (absolute risk difference 1.4%, 95% CI: 1.0%-1.8%), adjusting for confounders. Of this association 28.5% was an indirect effect via risk factors (absolute risk difference 0.4%, 95% CI: 0.3%-0.5%), while the indirect effect via stroke prevention drugs was negligible.

Conclusion: Almost one third of the association between low education and severe stroke was explained by risk factors, and clinical effort should be taken to reduce these risk factors to decrease stroke severity among those with low socioeconomic status.

Place, publisher, year, edition, pages
Public Library of Science, 2022
National Category
Public Health, Global Health and Social Medicine Probability Theory and Statistics
Identifiers
urn:nbn:se:umu:diva-197294 (URN)10.1371/journal.pone.0270533 (DOI)000892027900173 ()35749530 (PubMedID)2-s2.0-85132837107 (Scopus ID)
Funder
Swedish Research Council, 2018-02670Forte, Swedish Research Council for Health, Working Life and Welfare, 2018-00852
Available from: 2022-06-27 Created: 2022-06-27 Last updated: 2025-02-20Bibliographically approved
Lindmark, A. (2021). Neighborhood Socioeconomic Differences in Stroke Risk?: Highlighting the Need for Further Research. Neurology, 96(19), 879-880
Open this publication in new window or tab >>Neighborhood Socioeconomic Differences in Stroke Risk?: Highlighting the Need for Further Research
2021 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 96, no 19, p. 879-880Article in journal, Editorial material (Refereed) Published
Place, publisher, year, edition, pages
American Academy of Neurology, 2021
National Category
Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:umu:diva-182994 (URN)10.1212/WNL.0000000000011887 (DOI)33766990 (PubMedID)2-s2.0-85107090550 (Scopus ID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2018-00852Swedish Research Council, 2018-02670
Available from: 2021-05-11 Created: 2021-05-11 Last updated: 2025-02-20Bibliographically approved
Lindmark, A., Norrving, B. & Eriksson, M. (2020). Socioeconomic status and survival after stroke: using mediation and sensitivity analyses to assess the effect of stroke severity and unmeasured confounding. BMC Public Health, 20, Article ID 554.
Open this publication in new window or tab >>Socioeconomic status and survival after stroke: using mediation and sensitivity analyses to assess the effect of stroke severity and unmeasured confounding
2020 (English)In: BMC Public Health, E-ISSN 1471-2458, Vol. 20, article id 554Article in journal (Refereed) Published
Abstract [en]

Background: Although it has been established that low socioeconomic status is linked to increased risk of death after stroke, the mechanisms behind this link are still unclear. In this study we aim to shed light on the relationship between income level and survival after stroke by investigating the extent to which differences in stroke severity account for differences in survival.

Methods: The study was based on patients registered in Riksstroke (the Swedish stroke register) with first time ischemic stroke (n = 51,159) or intracerebral hemorrhage (n = 6777) in 2009–2012. We used causal mediation analysis to decompose the effect of low income on 3-month case fatality into a direct effect and an indirect effect due to stroke severity. Since causal mediation analysis relies on strong assumptions regarding residual confounding of the relationships involved, recently developed methods for sensitivity analysis were used to assess the robustness of the results to unobserved confounding.

Results: After adjustment for observed confounders, patients in the lowest income tertile had a 3.2% (95% CI: 0.9–5.4%) increased absolute risk of 3-month case fatality after intracerebral hemorrhage compared to patients in the two highest tertiles. The corresponding increase for case fatality after ischemic stroke was 1% (0.4–1.5%). The indirect effect of low income, mediated by stroke severity, was 1.8% (0.7–2.9%) for intracerebral hemorrhage and 0.4% (0.2–0.6%) for ischemic stroke. Unobserved confounders affecting the risk of low income, more severe stroke and case fatality in the same directions could explain the indirect effect, but additional adjustment to observed confounders did not alter the conclusions.

Conclusions: This study provides evidence that as much as half of income-related inequalities in stroke case fatality is mediated through differences in stroke severity. Targeting stroke severity could therefore lead to a substantial reduction in inequalities and should be prioritized. Sensitivity analysis suggests that additional adjustment for a confounder of greater impact than age would be required to considerably alter our conclusions.

Place, publisher, year, edition, pages
BioMed Central, 2020
Keywords
stroke, income, socioeconomic factors, mediation, direct effect, indirect effect, sensitivity analysis, unmeasured confounding
National Category
Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:umu:diva-170100 (URN)10.1186/s12889-020-08629-1 (DOI)000530278700004 ()32334556 (PubMedID)2-s2.0-85084031107 (Scopus ID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2018-00852Swedish Research Council, 2018-02670
Available from: 2020-04-27 Created: 2020-04-27 Last updated: 2025-02-20Bibliographically approved
Principal InvestigatorLindmark, Anita
Coordinating organisation
Umeå University
Funder
Period
2019-01-01 - 2022-12-31
National Category
Probability Theory and StatisticsPublic Health, Global Health, Social Medicine and EpidemiologyOther Medical Sciences not elsewhere specified
Identifiers
DiVA, id: project:1584Project, id: 2018-02670_VR