Serum Insulin-like Growth Factor-II Is Associated with Poor Poststroke Outcomes in Males: A Secondary Analysis

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Abstract
The insulin-like growth factor (IGF) system has significance for poststroke outcomes. Previously, we reported that low serum IGF-II (s-IGF-II) in the acute phase is associated with poststroke mortality, and that IGF-II is lower among males. Given the known interactions of the IGF system and estrogen receptor signaling, s-IGF-II may have sex-specific effects. In this study, we conducted a secondary analysis of sex differences in s-IGF-II and poststroke functional outcomes and mortality after ischemic stroke (IS) in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS, males; n = 315, females; n = 177). Functional outcomes were assessed using the modified Rankin scale (mRS) at 3 months and 2 years poststroke. Survival was recorded for 7 years or until death. Males in the lowest quintile of acute s-IGF-II had a higher poststroke mortality, with a crude hazard ratio [HR] of 2.52 (95% confidence interval [CI]) 1.59–3.99) and an adjusted HR of 1.83 (95% CI 1.09–3.06). No corresponding significant association was observed in females. Although acute s-IGF-II was crudely associated with poor functional outcomes among males after 3 months and 2 years, these associations were not independent of initial stroke severity in adjusted models. In conclusion, low levels of acute s-IGF-II are linked with poststroke mortality among males, but not significantly in females. Further studies are, however, warranted with sex hormone analysis, consideration of specific cause of death, and more females.
Funding Information
  • Swedish state under the agreement between the Swedish government and the County Councils, the ALF agreement (ALFGBG-1005813, 2021-01114, 20220184)
  • Swedish Medical Society (Svenska Läkaresällskapet) (ALFGBG-1005813, 2021-01114, 20220184)
  • Swedish Research Council (ALFGBG-1005813, 2021-01114, 20220184)
  • Swedish Heart Lung Foundation (ALFGBG-1005813, 2021-01114, 20220184)
  • Swedish Stroke Association (ALFGBG-1005813, 2021-01114, 20220184)
  • Göteborg Foundation for Neurological Research (ALFGBG-1005813, 2021-01114, 20220184)
  • Rune and Ulla Amlöv, Edit Jacobson, Magnus Bergvall, Emelle, Lars Hierta, and the John and Brit Wennerström Foundations (ALFGBG-1005813, 2021-01114, 20220184)

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