Family history of stroke and cardiovascular diseases in early-onset cryptogenic ischaemic stroke
(2026) In European Stroke Journal 11(3).- Abstract
BACKGROUND: Familial aggregation of stroke is well-documented, yet few studies have examined associations between stroke subtypes-particularly early-onset cryptogenic ischaemic stroke (eCIS)-and broader family history (FH) of cardiovascular disease. Such associations may provide insights into underlying etiologic mechanisms. METHODS: In this multicentre case-control study, we included eCIS patients aged 18-49 years and matched stroke-free controls. We analysed the association between FH of stroke, venous thromboembolism (VTE), coronary artery disease (CAD), aneurysms and eCIS using multivariable logistic regression, with a subgroup analysis stratifying patients by high-risk patent foramen ovale (HR-PFO). RESULTS: We enrolled 508 eCIS... (More)
BACKGROUND: Familial aggregation of stroke is well-documented, yet few studies have examined associations between stroke subtypes-particularly early-onset cryptogenic ischaemic stroke (eCIS)-and broader family history (FH) of cardiovascular disease. Such associations may provide insights into underlying etiologic mechanisms. METHODS: In this multicentre case-control study, we included eCIS patients aged 18-49 years and matched stroke-free controls. We analysed the association between FH of stroke, venous thromboembolism (VTE), coronary artery disease (CAD), aneurysms and eCIS using multivariable logistic regression, with a subgroup analysis stratifying patients by high-risk patent foramen ovale (HR-PFO). RESULTS: We enrolled 508 eCIS patients (182 [36%] with HR-PFO) and 520 controls. Compared with controls, patients more frequently reported FH of stroke among first-degree relatives (FDR) (20% vs. 14%, P = .01) and grandparents (47% vs. 39%, P = .01), FH of early-onset stroke among FDR (5% vs. 2%, P = .01) and FH of early-onset VTE among FDR (5% vs. 2%, P = .003). In adjusted analyses, eCIS was associated with FH of stroke among FDR (OR 1.50; 95% CI, 1.04-2.16) and grandparents (1.50; 1.12-1.99), with FH of early-onset stroke among FDR (2.36; 1.11-5.04); and with FH of early-onset VTE among FDR (3.45; 1.47-8.13). eCIS was also associated with FH of VTE among FDR (1.80, 1.09-2.98) in the presence of HR-PFO. FH of CAD or aneurysms was not associated with eCIS. CONCLUSION: FH of stroke and VTE, particularly early-onset events and in the presence of HR-PFO, are associated with eCIS. These findings support familial predisposition and highlight prothrombotic mechanisms in eCIS. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov/study/NCT01934725.
(Less)
- author
- Sihvo, Maximilian C.
; Ylikotila, Pauli
; Zedde, Marialuisa
; Pascarella, Rosario
; Sarkanen, Tomi
; Jatužis, Dalius
; Ryliškienė, Kristina
; von Sarnowski, Bettina
; Licenik, Radim
; Ferdinand, Phillip
; Kõrv, Janika
; Kõrv, Liisa
; Pezzini, Alessandro
; Fonseca, Ana Catarina
; Paula, André
; Martínez-Sánchez, Patricia
; Yesilot, Nilufer
; Fromm, Annette
; Waje-Andreassen, Ulrike
; Redfors, Petra
; Jood, Katarina
; Huhtakangas, Juha
; Sairanen, Tiina
; Hedman, Marja
; Jäkälä, Pekka
; Ten Cate, Hugo
; Gerdts, Eva
; Lehto, Mika
; Sinisalo, Juha
; Kittner, Steven J.
; Mitchell, Braxton D.
; Lindgren, Arne G.
LU
; Ilinca, Andreea
LU
; Putaala, Jukka
and Tomppo, Liisa
(Less) - organization
- publishing date
- 2026-03-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cryptogenic, family history, ischaemic stroke, PFO, young stroke
- in
- European Stroke Journal
- volume
- 11
- issue
- 3
- publisher
- SAGE Publications
- external identifiers
-
- scopus:105032622739
- pmid:41792039
- ISSN
- 2396-9881
- DOI
- 10.1093/esj/aakag013
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © The Author(s) 2026. Published by Oxford University Press on behalf of the European Stroke Organisation.
- id
- 35b706d5-3953-4924-864e-6d7326b4afdf
- date added to LUP
- 2026-05-06 16:29:00
- date last changed
- 2026-05-20 17:26:28
@article{35b706d5-3953-4924-864e-6d7326b4afdf,
abstract = {{<p>BACKGROUND: Familial aggregation of stroke is well-documented, yet few studies have examined associations between stroke subtypes-particularly early-onset cryptogenic ischaemic stroke (eCIS)-and broader family history (FH) of cardiovascular disease. Such associations may provide insights into underlying etiologic mechanisms. METHODS: In this multicentre case-control study, we included eCIS patients aged 18-49 years and matched stroke-free controls. We analysed the association between FH of stroke, venous thromboembolism (VTE), coronary artery disease (CAD), aneurysms and eCIS using multivariable logistic regression, with a subgroup analysis stratifying patients by high-risk patent foramen ovale (HR-PFO). RESULTS: We enrolled 508 eCIS patients (182 [36%] with HR-PFO) and 520 controls. Compared with controls, patients more frequently reported FH of stroke among first-degree relatives (FDR) (20% vs. 14%, P = .01) and grandparents (47% vs. 39%, P = .01), FH of early-onset stroke among FDR (5% vs. 2%, P = .01) and FH of early-onset VTE among FDR (5% vs. 2%, P = .003). In adjusted analyses, eCIS was associated with FH of stroke among FDR (OR 1.50; 95% CI, 1.04-2.16) and grandparents (1.50; 1.12-1.99), with FH of early-onset stroke among FDR (2.36; 1.11-5.04); and with FH of early-onset VTE among FDR (3.45; 1.47-8.13). eCIS was also associated with FH of VTE among FDR (1.80, 1.09-2.98) in the presence of HR-PFO. FH of CAD or aneurysms was not associated with eCIS. CONCLUSION: FH of stroke and VTE, particularly early-onset events and in the presence of HR-PFO, are associated with eCIS. These findings support familial predisposition and highlight prothrombotic mechanisms in eCIS. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov/study/NCT01934725.</p>}},
author = {{Sihvo, Maximilian C. and Ylikotila, Pauli and Zedde, Marialuisa and Pascarella, Rosario and Sarkanen, Tomi and Jatužis, Dalius and Ryliškienė, Kristina and von Sarnowski, Bettina and Licenik, Radim and Ferdinand, Phillip and Kõrv, Janika and Kõrv, Liisa and Pezzini, Alessandro and Fonseca, Ana Catarina and Paula, André and Martínez-Sánchez, Patricia and Yesilot, Nilufer and Fromm, Annette and Waje-Andreassen, Ulrike and Redfors, Petra and Jood, Katarina and Huhtakangas, Juha and Sairanen, Tiina and Hedman, Marja and Jäkälä, Pekka and Ten Cate, Hugo and Gerdts, Eva and Lehto, Mika and Sinisalo, Juha and Kittner, Steven J. and Mitchell, Braxton D. and Lindgren, Arne G. and Ilinca, Andreea and Putaala, Jukka and Tomppo, Liisa}},
issn = {{2396-9881}},
keywords = {{cryptogenic; family history; ischaemic stroke; PFO; young stroke}},
language = {{eng}},
month = {{03}},
number = {{3}},
publisher = {{SAGE Publications}},
series = {{European Stroke Journal}},
title = {{Family history of stroke and cardiovascular diseases in early-onset cryptogenic ischaemic stroke}},
url = {{http://dx.doi.org/10.1093/esj/aakag013}},
doi = {{10.1093/esj/aakag013}},
volume = {{11}},
year = {{2026}},
}