Stress Hyperglycemia Ratio and Adverse Outcomes in Acute Mild Ischemic Stroke or High-Risk Transient Ischemic Attack: A Secondary Analysis of the INSPIRES Trial

BACKGROUND: Evidence on the association between the stress hyperglycemia ratio (SHR) and adverse outcomes in patients with mild ischemic stroke (IS) or high-risk transient ischemic attack remains limited. METHODS: This was a secondary analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial. SHR was calculated as admission blood glucose (mmol/L) divided by (1.59* HbA1c [%]-2.59). Multivariable Cox regression models were used to assess the association between SHR and adverse clinical outcomes, adjusting for age, sex, and other potential factors. The primary efficacy outcome was any stroke (ischemic or hemorrhagic) within 90 days. Secondary efficacy outcomes comprised composite vascular events, recurrent IS, poor functional outcome, and early neurological deterioration. The primary safety outcome was moderate-to-severe bleeding within 90 days. RESULTS: The INSPIRES trial, ultimately enrolled 6100 patients with mild IS or high-risk transient ischemic attack caused by intracranial or extracranial atherosclerosis, of whom 4515 were included in this secondary analysis. The median age was 65 years (interquartile range, 57-71), and 2894 (64.10%) were male. During the 90-day follow-up, recurrent stroke occurred in 356 patients (7.88%), composite vascular events in 363 (8.04%), recurrent IS in 340 (7.53%), poor functional outcome in 474 (10.51%), and early neurological deterioration in 196 (4.34%). After adjustment for conventional confounders, compared with patients in the lower SHR group (Q1), those with higher SHR levels (Q4) had significantly increased risks of recurrent stroke (hazard ratio [HR], 1.84 [95% CI, 1.30-2.61]), composite vascular events (HR, 1.72 [95% CI, 1.22-2.41]), recurrent IS (HR, 1.79 [95% CI, 1.25-2.55]), poor functional outcome (HR, 1.56 [95% CI, 1.13-2.15]), and early neurological deterioration (HR, 1.62 [95% CI, 1.00-2.61]). In contrast, SHR was not significantly associated with any safety outcomes. CONCLUSIONS: Among patients with acute mild IS or high-risk transient ischemic attack of presumed atherosclerotic cause, elevated SHR levels were independently associated with increased risks of recurrent stroke, composite vascular events, recurrent IS, poor functional outcome, and early neurological deterioration.