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

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. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov/study/NCT01934725.