Trigger Factors for Stroke in Young Adults: A Case-Crossover Study

Merel S Ekker*, Jamie Inge Verhoeven, Karlijn Rensink, Mijntje M I Schellekens, Esther Boot, Mayte van Alebeek, Paul J A M Brouwers, Renate Arntz, Gert W van Dijk, Rob A R Gons, Inge van Uden, Tom den Heijer, Paul de Kort, Karlijn de Laat, Anouk Gw van Norden, Sarah Vermeer, Marian van Zagten, Robert van Oostenbrugge, Marieke J H Wermer, Paul NederkoornHenk Kerkhoff, Fergus Rooyer, Frank G van Rooij, Ido van den Wijngaard, Catharina Jm Klijn, Anil M Tuladhar, Frank-Erik de Leeuw

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND AND OBJECTIVES: Causes of stroke in young adults differ from those in the elderly, and in a larger percentage no cause can be determined. To gain more insight in the etiology of (cryptogenic) stroke in the young, we investigated whether trigger factors, such as short-lasting exposure to toxins or infection, may play a role.

METHODS: Patients aged 18-49 years with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) in 17 participating centers in the Netherlands completed a questionnaire about exposure to nine potential trigger factors in hazard periods and on a regular yearly basis. A case-crossover design was used to assess relative risks (RR) with 95% confidence intervals (95% CI) by the Mantel-Haenszel case-crossover method, for any stroke (ischemic stroke and ICH combined) and for different etiologic subgroups of ischemic stroke.

RESULTS: 1146 patients completed the questionnaire (1043 patients with an ischemic stroke, 103 with an ICH, median age 44.0 years, 52.6% men). For any stroke an increased risk emerged within one hour of cola consumption (RR 2.0, 95% CI 1.5-2.8) and vigorous physical exercise (RR 2.6, 95% CI 2.2-3.0), within two hours after sexual activity (RR 2.4, 95% CI 1.6-3.5), within 4 hours after illicit drug use (RR 2.8, 95% CI 1.7-4.9) and within 24 hours after fever or flu-like disease (RR 14.1, 95% CI 10.5-31.2; RR 13.9, 95% CI 8.9-21.9). Four trigger factors increased the risk of other determined and cryptogenic ischemic stroke, three that of cardio-embolic stroke, two that of large vessel atherosclerosis and likely atherothrombotic stroke combined and stroke with multiple causes, none that of stroke due to small vessel disease.

DISCUSSION: We identified cola consumption, vigorous physical exercise, sexual activity, illicit drug use, fever- and flu-like disease as potential trigger factors for stroke in the young, and found differences in type and number of trigger factors associated with different etiologic subgroups of ischemic stroke. These findings might help in better understanding the pathophysiological mechanisms of (cryptogenic) stroke in the young.

Original languageEnglish
Pages (from-to)E49-E61
Number of pages13
Issue number1
Early online date20 Sept 2022
Publication statusPublished - 3 Jan 2023


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