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.
Family history of stroke and cardiovascular diseases in early-onset cryptogenic ischaemic stroke / Sihvo, Mc; Ylikotila, P; Zedde, M; Pascarella, R; Sarkanen, T; Jatužis, D; Ryliškienė, K; Von Sarnowski, B; Licenik, R; Ferdinand, P; Kõrv, J; Kõrv, L; Pezzini, A; Fonseca, Ac; Paula, A; Martínez-Sánchez, P; Yesilot, N; Fromm, A; Waje-Andreassen, U; Redfors, P; Jood, K; Huhtakangas, J; Sairanen, T; Hedman, M; Jäkälä, P; Ten Cate, H; Gerdts, E; Lehto, M; Sinisalo, J; Kittner, Sj; Mitchell, Bd; Lindgren, Ag; Ilinca, A; Putaala, J; Tomppo, L. - In: EUROPEAN STROKE JOURNAL. - ISSN 2396-9881. - (2026). [10.1093/esj/aakag013]
Family history of stroke and cardiovascular diseases in early-onset cryptogenic ischaemic stroke
Pezzini A;
2026-01-01
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 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
