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Research Article
July 21, 2023
continuing medical education

Added Predictive Value of Female-Specific Factors and Psychosocial Factors for the Risk of Stroke in Women Under 50

August 22, 2023 issue
101 (8) e805-e814
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Abstract

Background and Objectives

Female-specific factors and psychosocial factors may be important in the prediction of stroke but are not included in prediction models that are currently used. We investigated whether addition of these factors would improve the performance of prediction models for the risk of stroke in women younger than 50 years.

Methods

We used data from the Stichting Informatievoorziening voor Zorg en Onderzoek, population-based, primary care database of women aged 20–49 years without a history of cardiovascular disease. Analyses were stratified by 10-year age intervals at cohort entry. Cox proportional hazards models to predict stroke risk were developed, including traditional cardiovascular factors, and compared with models that additionally included female-specific and psychosocial factors. We compared the risk models using the c-statistic and slope of the calibration curve at a follow-up of 10 years. We developed an age-specific stroke risk prediction tool that may help communicating the risk of stroke in clinical practice.

Results

We included 409,026 women with a total of 3,990,185 person-years of follow-up. Stroke occurred in 2,751 women (incidence rate 6.9 [95% CI 6.6–7.2] per 10,000 person-years). Models with only traditional cardiovascular factors performed poorly to moderately in all age groups: 20–29 years: c-statistic: 0.617 (95% CI 0.592–0.639); 30–39 years: c-statistic: 0.615 (95% CI 0.596–0.634); and 40–49 years: c-statistic: 0.585 (95% CI 0.573–0.597). After adding the female-specific and psychosocial risk factors to the reference models, the model discrimination increased moderately, especially in the age groups 30–39 (Δc-statistic: 0.019) and 40–49 years (Δc-statistic: 0.029) compared with the reference models, respectively.

Discussion

The addition of female-specific factors and psychosocial risk factors improves the discriminatory performance of prediction models for stroke in women younger than 50 years.

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Information & Authors

Information

Published In

Neurology®
Volume 101Number 8August 22, 2023
Pages: e805-e814
PubMed: 37479530

Publication History

Received: August 26, 2022
Accepted: April 25, 2023
Published online: July 21, 2023
Published in issue: August 22, 2023

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Disclosure

The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Study Funding

M.J.H. Wermer was supported by a personal Vidi and Aspasia grant from ZonMw/NWO (91717337) and a Dekker Clinical Established Investigator Grant from the Dutch Heart Foundation (2016T86). Dr. Van Os was funded by a personal Dekker Junior Clinical Scientist Grant (2018T082) and the Innovation Grant (2018T016) from the Dutch Heart Foundation and a ZonMw Gender & Prevention Grant (555003014).

Authors

Affiliations & Disclosures

Hendrikus J.A. van Os, MD, PhD
From the Department of Neurology (H.J.A.v.O., M.D.F., M.J.H.W.), National eHealth Living Lab (H.J.A.v.O.), Departments of Public Health & Primary Care/Health Campus The Hague (H.J.v.A.O., T.N.B., J.M.K., H.M.M.V., R.C.V.), Clinical Epidemiology (R.H.H.G.), and Biomedical Data Sciences (H.P., R.H.H.G.), Leiden University Medical Center; Department of Neurology (J.P.K.), University Medical Center Utrecht; and Department of Neurology (M.J.H.W.), University Medical Center Groningen, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Dr. Van Os was funded by a personal Dekker Junior Clinical Scientist Grant (2018T082) and the Innovation Grant (2018T016) from the Dutch Heart Foundation, and a ZonMw Gender & Prevention Grant (555003014).
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Jos P. Kanning, MSc
From the Department of Neurology (H.J.A.v.O., M.D.F., M.J.H.W.), National eHealth Living Lab (H.J.A.v.O.), Departments of Public Health & Primary Care/Health Campus The Hague (H.J.v.A.O., T.N.B., J.M.K., H.M.M.V., R.C.V.), Clinical Epidemiology (R.H.H.G.), and Biomedical Data Sciences (H.P., R.H.H.G.), Leiden University Medical Center; Department of Neurology (J.P.K.), University Medical Center Utrecht; and Department of Neurology (M.J.H.W.), University Medical Center Groningen, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Michel D. Ferrari, MD, PhD
From the Department of Neurology (H.J.A.v.O., M.D.F., M.J.H.W.), National eHealth Living Lab (H.J.A.v.O.), Departments of Public Health & Primary Care/Health Campus The Hague (H.J.v.A.O., T.N.B., J.M.K., H.M.M.V., R.C.V.), Clinical Epidemiology (R.H.H.G.), and Biomedical Data Sciences (H.P., R.H.H.G.), Leiden University Medical Center; Department of Neurology (J.P.K.), University Medical Center Utrecht; and Department of Neurology (M.J.H.W.), University Medical Center Groningen, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
ENJ Associate Editor
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Tobias N. Bonten, MD, PhD
From the Department of Neurology (H.J.A.v.O., M.D.F., M.J.H.W.), National eHealth Living Lab (H.J.A.v.O.), Departments of Public Health & Primary Care/Health Campus The Hague (H.J.v.A.O., T.N.B., J.M.K., H.M.M.V., R.C.V.), Clinical Epidemiology (R.H.H.G.), and Biomedical Data Sciences (H.P., R.H.H.G.), Leiden University Medical Center; Department of Neurology (J.P.K.), University Medical Center Utrecht; and Department of Neurology (M.J.H.W.), University Medical Center Groningen, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Janet M. Kist, MD
From the Department of Neurology (H.J.A.v.O., M.D.F., M.J.H.W.), National eHealth Living Lab (H.J.A.v.O.), Departments of Public Health & Primary Care/Health Campus The Hague (H.J.v.A.O., T.N.B., J.M.K., H.M.M.V., R.C.V.), Clinical Epidemiology (R.H.H.G.), and Biomedical Data Sciences (H.P., R.H.H.G.), Leiden University Medical Center; Department of Neurology (J.P.K.), University Medical Center Utrecht; and Department of Neurology (M.J.H.W.), University Medical Center Groningen, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Hedwig M.M. Vos, MD, PhD
From the Department of Neurology (H.J.A.v.O., M.D.F., M.J.H.W.), National eHealth Living Lab (H.J.A.v.O.), Departments of Public Health & Primary Care/Health Campus The Hague (H.J.v.A.O., T.N.B., J.M.K., H.M.M.V., R.C.V.), Clinical Epidemiology (R.H.H.G.), and Biomedical Data Sciences (H.P., R.H.H.G.), Leiden University Medical Center; Department of Neurology (J.P.K.), University Medical Center Utrecht; and Department of Neurology (M.J.H.W.), University Medical Center Groningen, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Rimke C. Vos, PhD
From the Department of Neurology (H.J.A.v.O., M.D.F., M.J.H.W.), National eHealth Living Lab (H.J.A.v.O.), Departments of Public Health & Primary Care/Health Campus The Hague (H.J.v.A.O., T.N.B., J.M.K., H.M.M.V., R.C.V.), Clinical Epidemiology (R.H.H.G.), and Biomedical Data Sciences (H.P., R.H.H.G.), Leiden University Medical Center; Department of Neurology (J.P.K.), University Medical Center Utrecht; and Department of Neurology (M.J.H.W.), University Medical Center Groningen, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
Scientific board of my department for quality before it will be submitted to the ethical committee (non-commercial and non-profit).
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
Diabetesgeneeskunde, editorial member, writing summaries' of published articles for peers, years 2021-2022
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Hein Putter, PhD
From the Department of Neurology (H.J.A.v.O., M.D.F., M.J.H.W.), National eHealth Living Lab (H.J.A.v.O.), Departments of Public Health & Primary Care/Health Campus The Hague (H.J.v.A.O., T.N.B., J.M.K., H.M.M.V., R.C.V.), Clinical Epidemiology (R.H.H.G.), and Biomedical Data Sciences (H.P., R.H.H.G.), Leiden University Medical Center; Department of Neurology (J.P.K.), University Medical Center Utrecht; and Department of Neurology (M.J.H.W.), University Medical Center Groningen, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Rolf H.H. Groenwold, MD, PhD
From the Department of Neurology (H.J.A.v.O., M.D.F., M.J.H.W.), National eHealth Living Lab (H.J.A.v.O.), Departments of Public Health & Primary Care/Health Campus The Hague (H.J.v.A.O., T.N.B., J.M.K., H.M.M.V., R.C.V.), Clinical Epidemiology (R.H.H.G.), and Biomedical Data Sciences (H.P., R.H.H.G.), Leiden University Medical Center; Department of Neurology (J.P.K.), University Medical Center Utrecht; and Department of Neurology (M.J.H.W.), University Medical Center Groningen, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
None
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
PDS - associate editor (since Jan 2022)
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
None
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Marieke J.H. Wermer, PhD https://orcid.org/0000-0002-6838-9521
From the Department of Neurology (H.J.A.v.O., M.D.F., M.J.H.W.), National eHealth Living Lab (H.J.A.v.O.), Departments of Public Health & Primary Care/Health Campus The Hague (H.J.v.A.O., T.N.B., J.M.K., H.M.M.V., R.C.V.), Clinical Epidemiology (R.H.H.G.), and Biomedical Data Sciences (H.P., R.H.H.G.), Leiden University Medical Center; Department of Neurology (J.P.K.), University Medical Center Utrecht; and Department of Neurology (M.J.H.W.), University Medical Center Groningen, the Netherlands.
Disclosure
Scientific Advisory Boards:
1.
Scientific advisory board: CAA foundationDSMB Trident trial
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
None
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NWO/ZonMW Vidi and Aspasia grant
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Funding received from Netherlands Heart Foundation (unrelated to this manuscript)
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. van Os [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Editor-in-Chief José Merino, MD, MPhil, FAAN.

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  1. A single risk assessment for the most common diseases of ageing, developed and validated on 10 cohort studies, BMC Medicine, 22, 1, (2024).https://doi.org/10.1186/s12916-024-03711-6
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