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

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.