Family history of stroke and cardiovascular diseases in early-onset cryptogenic ischaemic stroke

Maximilian C Sihvo; Pauli Ylikotila; Marialuisa Zedde; Rosario Pascarella; Tomi Sarkanen; Dalius Jatužis; Kristina Ryliškienė; Bettina von Sarnowski; Radim Licenik; Phillip Ferdinand; Janika Kõrv; Liisa Kõrv; Alessandro Pezzini; Ana Catarina Fonseca; André Paula; Patricia Martínez-Sánchez; Nilufer Yesilot; Annette Fromm; Ulrike Waje-Andreassen; Petra Redfors; Katarina Jood; Juha Huhtakangas; Tiina Sairanen; Marja Hedman; Pekka Jäkälä; Hugo ten Cate; Eva Gerdts; Mika Lehto; Juha Sinisalo; Steven J Kittner; Braxton D Mitchell; Arne G Lindgren; Andreea Ilinca; Jukka Putaala; Liisa Tomppo

doi:10.1093/esj/aakag013

Title	Family history of stroke and cardiovascular diseases in early-onset cryptogenic ischaemic stroke
Authors	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 ; Ilinca, Andreea ; Putaala, Jukka ; Tomppo, Liisa
DOI	10.1093/esj/aakag013
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Is Part of	European stroke journal.. London : Oxford University Press. 2026, vol. 11, iss. 3, art. no. aakag013, p. [1-9].. ISSN 2396-9873. eISSN 2396-9881
Keywords [eng]	ischaemic stroke ; cryptogenic ; young stroke ; PFO ; family history
Abstract [eng]	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.
Published	London : Oxford University Press
Type	Journal article
Language	English
Publication date	2026
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„Family history of stroke and cardiovascular diseases in early-onset cryptogenic ischaemic stroke“