Abstract

Introduction: Hyperglycemia is associated with increased lesion volume and worse functional outcome after acute ischemic stroke, however, it is not known whether it is associated with further cerebrovascular events. The aim of this study was to examine the association between admission hyperglycemia and subsequent ischemic stroke. Methods: This was an exploratory analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which compared combined clopidogrel/aspirin with aspirin alone with respect to the primary outcome of subsequent ischemic stroke, myocardial infarction, or vascular death. We dichotomized patients based on a serum glucose threshold of 180mg/dl (chosen a priori based on the upper boundary of the active control arm of SHINE). We calculated hazard ratios (HR) for subsequent ischemic stroke at 90 days via a Cox proportional hazards model adjusting for age, sex, study treatment assignment and vascular risk factors. We performed sensitivity analyses excluding patients with a known history of diabetes and in patients whose index event was a TIA vs. minor stroke. Results: Of 4,878 patients in this analysis (mean age 64.6 years), 594 (12.2%) were hyperglycemic on presentation and 267 (5.5%) had a subsequent ischemic stroke within 90 days. Admission hyperglycemia was associated with subsequent ischemic stroke (HR 1.88; 95% CI:1.39-2.53, p<0.01). This association persisted after adjustment for relevant covariates (aHR 1.86, 95% CI: 1.37-2.52, p<0.01), in non-diabetic patients (n=3,529, aHR 3.1, 95% CI:1.7-5.7, p<0.01), in patients with TIA (n=2,327, aHR 2.2, 95% CI: 1.2-4.1, p<0.01), and in patients with minor ischemic stroke (n=2,304, aHR = 1.5, 95% CI: 1.1-2.2, p=0.02). Conclusions: Hyperglycemia portends a higher risk of subsequent ischemic stroke after adjusting for known predictors of stroke recurrence. This study may provide further support to pursuing aggressive secondary prevention strategies in this population.

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