Abstract

Background: Biomarkers may help identify patients most likely to benefit from therapies. We tested whether serum glial fibrillary acidic protein (GFAP), a biomarker elevated early after intracerebral hemorrhage (ICH) in response to blood-brain barrier disruption, is associated with hematoma expansion (HE) and outcome after ICH and whether GFAP levels modify the effect of factor VII treatment. Methods: We performed an exploratory analysis of the recombinant activated factor VII for acute ICH (FAST) trial. FAST collected serum GFAP levels were collected at admission within 4 hours of ICH onset prior to factor VII treatment. We used regression analyses to evaluate the associations between serum GFAP, HE (dichotomized as &gte; 33% or > 6 mL increase in ICH volume from baseline to 24h and as the absolute volume of expansion), and 3-month poor outcome (modified Rankin Scale score 4-6). We tested for interaction between GFAP and factor VII treatment by adding product terms to multivariable regression models. Results: Of 841 enrolled patients, we included 567 (67%) with available GFAP levels (mean age 64 [SD 13], female sex 203 [37%]). GFAP was associated with HE (adjusted odds ratio [OR] 1.54, 95% CI 1.10-2.17) and poor outcome (adjusted OR 1.86, 95% CI 1.18-3.09). Compared to patients in the lowest GFAP quartile, those in the highest quartile had 2 times the odds of HE (95% CI 1.08-3.89) and 2.7 times the odds of a poor outcome (95% CI 1.33-5.70). GFAP modified the association between factor VII treatment and HE volume (multivariable interaction p=0.04): treatment was not associated with reduced HE volume in the lowest GFAP quartile (β -0.44, 95% CI -3.54 to 2.67), but was associated with reduced HE volume in higher quartiles (β -3.82, 95% CI -7.58 to -0.06). Conclusions: In the FAST trial population, early GFAP levels were associated with HE and poor functional outcome. Factor VII treatment was associated with a greater reduction in HE volume in patients with higher GFAP levels. Serum GFAP may be useful for risk-stratifying patients early after ICH onset.

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