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

TL;DR

This study finds that a family history of stroke and blood clots is linked to early-onset cryptogenic stroke, suggesting inherited risks and clotting issues.

Contribution

The study identifies new associations between family history of stroke and VTE with early-onset cryptogenic ischaemic stroke.

Findings

eCIS patients had higher family history of stroke in first-degree relatives and grandparents.

Family history of early-onset VTE in first-degree relatives was strongly associated with eCIS.

Associations were stronger in patients with high-risk patent foramen ovale.

Abstract

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.

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).

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.

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.

www.clinicaltrials.gov/study/NCT01934725

Graphical Abstract

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