Association of time of onset of ischemic stroke with severity of presentation, acute progression, and long-term outcome: a cohort study
PLoS Med. 2022 Feb 4;19(2):e1003910. doi: 10.1371/journal.pmed.1003910. eCollection 2022 Feb.
BACKGROUND: Preclinical data suggest a circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with stroke onset in the inactive (day) phase than in active phase (night). We sought to examine the association of stroke onset time with severity of presentation, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke.
METHODS AND RESULTS: In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on baseline stroke severity (National Institutes of Health Stroke Scale [NIHSS] admission score), FIN and favorable functional result (modified Rankin scale at 3 months [mRS] score of 0 to 2 against 3 to 6). We included 17,461 consecutive patients who witnessed an ischemic stroke within 6 hours of onset. Time to onset of stroke was divided into 2 groups (day [06:00 to 18:00] versus early night [18:00 to 06:00]) and in 6 groups at 4 hour intervals. We used ordered or logistic mixed-effects regression models while accounting for clustering by hospital. The mean age was 66.9 (SD 13.4) years and 6,900 (39.5%) were female. END occurred in 2219 (12.7%) patients. After adjusting for covariates including age, gender, prior stroke, mRS score before stroke, NIHSS score at admission, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, antiplatelet drug use before stroke, statin use before stroke, revascularization, stroke onset season, and time from onset to arrival at hospital, stroke that occurred at night was more prone to NDT (adjusted incidence of 14.4% versus 12.8%, p=0.006) and had a lower probability of a favorable outcome (adjusted odds ratio, 0 .88 [95% CI, 0.79 to 0.98]; p = 0.03) compared to daytime stroke. When stroke onset times were grouped into 4-hour intervals, a monotonic gradient in the presentation of the NIHSS score was noted, going from a nadir at 06:00 a.m. to 10:00 a.m. to a peak at 02:00 a.m. to 06:00 a.m. Patients who had a stroke between 6:00 p.m. and 10:00 p.m. and between 10:00 p.m. and 2:00 a.m. were more likely to experience an END than patients who had a stroke between 6:00 a.m. and 10:00 a.m. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, going from a peak at 6:00 a.m. to 10:00 a.m. to a nadir at 10:00 p.m. to 2:00 a.m. Limitations of the study include lack of information on sleep disturbances and patients’ work/activity schedules.
CONCLUSIONS: Nocturnal strokes, compared to daytime strokes, are associated with higher neurological severity, more frequent END, and poorer functional outcome at 3 months. These results suggest that circadian time of onset is an important additional variable to include in natural history epidemiological studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.
PMID:35120123 | DOI:10.1371/journal.pmed.1003910