Association Between Recent Mechanical Risk Factors for Venous Thrombosis and Young-Onset Cryptogenic Ischemic Stroke

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BACKGROUND: In young adults, the risk factors (RFs) for cryptogenic ischemic stroke (CIS) remain unclear. We aimed to investigate the association between recent mechanical venous thrombosis RFs (VTRFs) and young-onset CIS in this multicenter sex- and age-matched case-control study. METHODS: Five hundred forty-six patients aged 18 to 49 years (median age, 41 [34-46] years; 47.3% women) with a recent CIS and 546 stroke-free community-based controls were included in the study across 19 European centers between October 2013 and November 2022. Mechanical VTRFs, including surgical treatment, nonsurgical intervention, injury, and immobilization occurring within 90 days prestroke, were assessed using standardized, structured interviews. Conditional logistic regression was used to assess the association of mechanical VTRFs with CIS. Age, sex, level of education, and traditional and nontraditional stroke RFs were included as confounders. RESULTS: Mechanical VTRFs within 14 days prestroke were more prevalent in cases than controls (15.4% versus 9.6%) and independently associated with CIS after adjustment for demographics and traditional stroke RFs (odds ratio [OR], 1.67 [95% CI, 1.05-2.67]). In age-stratified analysis, this association remained significant after additional adjustment for nontraditional RFs in 18- to 39-year-olds (OR, 2.36 [95% CI, 1.02-5.46]) but was not significant in the 40- to 49-year age group (OR, 1.50 [95% CI, 0.73-3.08]). In addition, mechanical VTRFs were associated with CIS in cases with clinically relevant patent foramen ovale in a fully adjusted model (OR, 2.06 [95% CI, 1.21-3.51]) but not in those without (OR, 1.29 [95% CI, 0.76-2.18]). No significant associations were observed for mechanical VTRFs occurring >14 days before stroke. Baseline blood thrombophilia markers did not differ between cases with and without mechanical VTRFs 0 to 14 or 15 to 90 days before stroke. CONCLUSIONS: Recent mechanical VTRFs occurring within 14 days preceding stroke contribute to the risk of young-onset CIS, particularly in younger individuals and those with a clinically relevant patent foramen ovale. This risk does not appear to be conveyed by thrombophilic factors assessed. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01934725.

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