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

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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Journal
Stroke
Published
2026-08-26
DOI
https://doi.org/10.1161/strokeaha.125.054299
Primary Topic
Cardiovascular and Diving-Related Complications
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article

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

Marco Ritelli, Odd Bech‐Hanssen, Tímea Szántó, Patricia Martínez‐Sánchez et al.
Stroke
Cardiovascular and Diving-Related Complications
article

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

Marco Ritelli, Odd Bech‐Hanssen, Tímea Szántó, Patricia Martínez‐Sánchez, Sahrai Saeed, Tomi Sarkanen, Tuuli Miettinen, Maria Davidson, Liisa Tomppo, Margareta Abrahamson, Riina Vibo, Nina Jaakonmäki, Külliki Karu, Georgios K. Tsivgoulis, Mine Sezgin, Carlo Mario Lombardi, Heli Tolppanen, Ossi Nerg, Bettina von Sarnowski, Pauli Ylikotila, Janne Rapola, Marialuisa Zedde, Ulla Junttola, De Paula A, Hugo Ten Cate, Marjaana Tiainen, Lotta Joutsi‐Korhonen, Radim Líčeník, Laura Kytövuori, Victoria Mejias Olmedo, Peter Owusu‐Agyei, Nilüfer Yeşilot, Mikael Jerndal, Aleksandra Ekkert, Petra Redfors, Kristina Ryliškienė, Zoltan Pencz, Tuukka Helin, Katarina Jood, Juha Sinisalo, Jukka Putaala A, Ana Catarina Fonseca, Marja Hedman, Diana Zakarkaitė, Heikki Numminen, Liisa Kõrv, Satu Suihko, Laura Amaya‐Pascasio, Lukas Holmegaard, Pekka A. Jäkälä, Phillip Ferdinand, Mika Lehto, Christine Roffe, Cheryl Oxley, Lauri Tulkki, Ulf Schminke, Dalius Jatužis, Raúl Reyes Parrilla, Nicolas Martinez‐Majander, Ulrike Waje‐Andreassen, Frank‐Erik de Leeuw, Alessandro Pezzini, Eva Gerdts, Essi Ryödi, Julija Valančienė, Teresa Grimaldi, Shakar Kutal, Muhammad Khaled Hasan, Santhosh Subramonian, Piibe Muda, Juha Huhtakangas, Janika Kõrv, Raila Busch, Esme Ekizoğlu Turgut, Mohammad Hacque, Rytis Masiliūnas, Sofie Abels, Maximillian Sihvo, Merel Ekker, Jaana Autere, Tiina Sairanen, Suzette Elias-Smale, Marko Virtanen, Lauri Soinne, Riikka Lautamäki, Annette Fromm, Jani Pirinen, Turgut Tatlisumak, Annika Nordanstig, Elvira Carrión Rios, Antti Saraste, Myrna M.E. van Dongen, Suvi Tuohinen
article en

Abstract

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.

Stroke
University of Parma (IT), University of Helsinki (FI), Radboud University Nijmegen (NL), Vilnius University (LT), University of Eastern Finland (FI), National and Kapodistrian University of Athens (GR), Oulu University Hospital (FI), Universitätsmedizin Greifswald (DE), University Hospitals of North Midlands NHS Trust (GB), Helsinki University Hospital (FI), Haukeland University Hospital (NO), Sahlgrenska University Hospital (SE), Turku University Hospital (FI), Tartu University Hospital (EE), Radboud University Medical Center (NL), Maastricht University (NL), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Kuopio University Hospital (FI), Surgical Specialties (Canada) (CA), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Pirkanmaa Hospital District (FI), Tampere University Hospital (FI), Tampere University (FI), University General Hospital Attikon (GR), Cambridgeshire and Peterborough NHS Foundation Trust (GB), Hospital de Santa Maria (PT), Complejo Hospitalario Torrecárdenas (ES), Hospital District of Helsinki and Uusimaa (FI), University of Bergen (NO), University of Tartu (EE), Istanbul University (TR), University of Brescia (IT), University of Gothenburg (SE)
Quality Education
Openalex Percentile: Top 11%
Cardiovascular and Diving-Related Complications
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