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Insulin-like growth factor (IGF) I, -II, and IGF binding protein-3 and risk of ischemic stroke.

Johnsen SP, Hundborg HH, Sørensen HT, Orskov H, Tjønneland A, Overvad K, Jørgensen JO

Department of Clinical Epidemiology, Aarhus University Hospital, Ole Worms Allé 150, DK-8000 Aarhus C, Denmark. spj@dce.au.dk

BACKGROUND: Low IGF-I levels may be associated with the development of stroke; however, prospective data appear to be unavailable. METHODS: This was a nested case-control study within a Danish follow-up study, including 57,053 men and women. Baseline data included circulating IGF-I, IGF-II, and IGF binding protein (IGFBP)-3 concentrations as well as lifestyle factors and medical history. We identified 254 cases with incident ischemic stroke and 254 gender- and age-matched controls. RESULTS: Participants in the bottom quartiles of IGF-I and IGFBP-3 levels (median concentrations, 72 and 2937 ng/ml, respectively) were at increased risk of ischemic stroke, e.g. adjusted odds ratios (ORs) of 2.06 [95% confidence interval (CI), 1.05-4.03] and 2.29 (95% CI, 1.17-4.49), respectively, when compared with participants in the top quartiles (median concentrations, 125 and 4835 ng/ml, respectively). A negative, although weaker, association was also found for IGF-II (adjusted OR 1.44, 95% CI 0.79-2.64) when comparing the bottom quartile with the top quartile. No substantial associations were seen for IGF-I and IGF-II when also adjusting for IGFBP-3; adjusting IGFBP-3 for IGF-I and -II had only a minor impact on the risk estimates. CONCLUSION: These findings give some support to the hypothesis that the IGF axis is involved in the pathogenesis of ischemic stroke.

Published 8 November 2005 in J Clin Endocrinol Metab, 90(11): 5937-41.
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