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

Department of Clinical Epidemiology (S.P.J., H.H.H., H.T.S., K.O.) and Medical Department M (Endocrinology and Diabetes) and Institute of Experimental Clinical Research (H.Ø., J.O.L.J.), Aarhus University Hospital, DK-8000 Aarhus, Denmark; Center for Cardiovascular Research (S.P.J., K.O.), Aalborg Hospital, Aarhus University Hospital, DK-9100 Aalborg, Denmark; and Institute of Cancer Epidemiology (A.T.), Danish Cancer Society, DK-2100 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Søren Paaske Johnsen, Ph.D., Department of Clinical Epidemiology, Aarhus University Hospital, Ole Worms Allé 150, DK-8000 Aarhus C, Denmark. E-mail: spj{at}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.

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