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This version published online on August 30, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-2088
A more recent version of this article appeared on November 1, 2005
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Submitted on October 22, 2004
Accepted on August 18, 2005

Insulin-Like Growth Factor (IGF) I, -II And IGF Binding Protein-3 And Risk Of Ischemic Stroke

S. P. Johnsen PhD*, H. H. Hundborg PhD, H. T. Sørensen DMSc, H. Ørskov DMSc, A. Tjønneland PhD, K. Overvad PhD, and J. O.L. Jørgensen DMSc

From Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark (S.P.J., H.H.H., K.O., H.T.S.), Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark (S.P.J., K.O.), Medical Department M (Endocrinology and Diabetes) and Institute of Experimental Clinical Research, Aarhus University Hospital, Aarhus, Denmark (H.Ø., J.O.L.J.) and Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark (A.T.)

* To whom correspondence should be addressed. E-mail: spj{at}dce.au.dk.

Background: Low insulin-like growth factor I (IGF-I) levels may be associated with the development of stroke; however, prospective data appear not to be available. Methods: 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 (BP)-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 2,937 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 4,835 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 -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.




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