Abstract A067: Diurnal Variation in Acute Ischemic Stroke Severity and Outcomes: Insights from the Get With The Guidelines Registry

Background: Preclinical models demonstrate circadian biology influences ischemic brain injury with accelerated infarct growth during the inactive phase. Whether this translates to humans is unclear. We analyzed the national US Get With the Guidelines (GWTG) – Stroke registry to assess diurnal (time-of-day) variations in AIS onset and patient outcomes. Methods: We identified all 2015-2023 AIS discharges from GWTG – Stroke hospitals. Multivariable mixed-effect logistic regression and univariable sinusoidal regression analyses were used to determine the associations between AIS onset time and discharge outcomes [global disability (mRS), ambulatory status, discharge destination, mortality]. We adjusted for 30 patient-level variables: demographics, medical history, AIS factors, 6 hospital-level variables. AIS onset time was analyzed as dichotomous [daytime (07:00-22:59) vs nighttime (23:00-06:59)]; in six 4-hour blocks; and as a continuous variable. Results: Among 1,398,777 patients from 2,593 hospitals, median age was 71 (IQR 61-81), 48.8% were women, mean presenting NIHSS was 6.4 (±7.2), and 24.54% received IV thrombolysis. AIS incidence varied nearly 3-fold by time-of-day with a peak in the late morning to early afternoon (09:00-13:00) (Fig 1). Presenting NIHSS varied modestly with onset time, with a mean of 6.1 in the morning (07:00-10:59) to 6.6 in the late evening (19:00-22:59) ( p <0.0001). After adjusting for potential confounders, daytime AIS onset was associated with lower mortality risk (OR=0.92, 95% CI: 0.90-0.95) and better discharge functional outcomes (mRS 0-2: OR=1.08, 95% CI: 1.06-1.10; independent or assisted ambulation: OR=1.09, 95% CI: 1.07-1.11). Patients with daytime-onset-AIS were less likely to be discharged home or to inpatient rehab (OR=0.97, 95% CI: 0.95-0.98). Analyzing onset-time as a continuous variable and outcomes as ordinal variables, onset time was associated with a sinusoidal variation of modest amplitude in levels of global disability and discharge ambulatory status. The best outcomes were around 13:00-13:30 and the worst outcomes were around 01:00-1:30 (Fig 2 and 3). Conclusion: Nighttime-onset AIS is associated with higher presenting NIHSS, increased mortality, and worse discharge functional outcomes compared to daytime-onset AIS. These results suggest diurnal factors influence cerebrovascular pathophysiology and stroke recovery. Time-of-onset may serve as an informative variable in future AIS studies and treatment trials.