Published Online
on April 20, 2006

A more recent version of this article appeared on June 1, 2006

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Submitted on October 12, 2005
Revised on January 19, 2006
Accepted on March 2, 2006

Impaired Glucose Tolerance Increases Stroke Risk in Nondiabetic Patients With Transient Ischemic Attack or Minor Ischemic Stroke

Sarah E. Vermeer MD, PhD^*; Willemijn Sandee MSc; Ale Algra MD, FAHA; Peter J. Koudstaal MD, PhD; L. Jaap Kappelle MD, PhD; Diederik W.J. Dippel MD, PhD; on behalf of the Dutch TIA Trial Study Group

From the Department of Neurology (S.E.V., W.S., P.J.K., D.W.J.D.), Erasmus Medical Center, Rotterdam; and the Department of Neurology (A.A., L.J.K.), University Medical Center Utrecht, The Netherlands.

^* To whom correspondence should be addressed. E-mail: s.vermeer{at}erasmusmc.nl.

Background and Purpose--Impaired glucose tolerance, an intermediate metabolic state between normal glucose and diabetes characterized by nonfasting glucose levels between 7.8 to 11.0 mmol/L, is associated with an increased stroke risk in patients with coronary heart disease. Whether impaired glucose tolerance increases the risk of stroke in patients with transient ischemic attack (TIA) or minor ischemic stroke is unknown.

Methods--In total, 3127 patients with a TIA or minor ischemic stroke participated in the Dutch TIA Trial, testing 2 different doses of aspirin and atenolol versus placebo. We estimated the risk of stroke and the risk of myocardial infarction or cardiac death in relation to baseline nonfasting glucose levels (mean 6.0, SD 2.2 mmol/L) with Cox proportional hazards regression analysis, adjusted for cardiovascular risk factors.

Results--During 2.6 years follow-up, 272 patients (9%) experienced a stroke and 200 (6%) a myocardial infarction or cardiac death. We found a J-shaped relationship between baseline nonfasting glucose levels and stroke risk. Stroke risk was nearly doubled in patients with impaired glucose tolerance (glucose 7.8 to 11.0 mmol/L) compared with those with normal glucose levels (hazard ratio [HR] 1.8, 95% CI, 1.1 to 3.0) and nearly tripled in diabetic patients (glucose 11.1 mmol/L; HR 2.8, 95% CI, 1.9 to 4.1). Patients with low glucose levels (<4.6 mmol/L) had a 50% increased stroke risk (HR 1.5, 95% CI, 1.0 to 2.2) compared with those with normal glucose levels. There was no association between glucose levels and risk of myocardial infarction or cardiac death.

Conclusion--Impaired glucose tolerance is an independent risk factor for future stroke in nondiabetic patients with TIA or minor ischemic stroke.

Key words: glucose • glucose intolerance • risk • transient ischemic attack

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