Abstract Background and aims The incidence, severity, progression, and long-term outcome of acute ischemic stroke vary across the 24-hour day. Data on the link between patients’ circadian chronotype, e.g. morningness (“larks”) and eveningness (“owls”), and stroke, however, are missing. We aim to characterize the association of chronotype with presentation and outcome of patients with acute cerebral ischemia. Methods The CIRCA Chronotype and Stroke Registry is a prospective observational study enrolling adult patients within 24 hours of last-known-well time across five centers in the United States and Europe. Chronotypes (sleep timing midpoints on work-free days) were assessed using the Ultra-Short Munich Chronotype Questionnaire. Associations between chronotype and baseline NIHSS score/functional outcome (mRS score) were assessed through multiple linear/logistic regression respectively. Results 691 patients (median age 71 years, 41% female) were enrolled from February 2024 to February 2026. Chronotypes between 02:31 and 03:30 were the most prevalent (35.5%) (Fig. 1). Early chronotypes were older and more frequently hypertensive than intermediate and late chronotypes (Table 1). Earlier chronotype was associated with higher NIHSS at presentation independent of age (β −0.51; 95% CI - 0.91 to −0.12; p=0.01) (Fig. 2) and with worse functional outcomes at day 90 (OR 0.69; 95% CI 0.54 - 0.86; p=b 0.001), persistent after additional adjustment for baseline NIHSS (OR 0.75; 95% CI 0.59 - 0.95; p=0.02) and other variables (Fig. 3). Conclusions Our study links early chronotype to higher stroke severity and poorer functional outcomes, providing evidence for relationship(s) between chronobiology and stroke. Further studies should investigate mechanisms and potential treatment-effect modification. Conflict of interest Table 1 - belongs to Conclusions Figure 1 - belongs to Conclusions Figure 2 - belongs to Conclusions Figure 3 - belongs to Conclusions
Veloudiou et al. (2026) studied this question.