Circulating granulocyte colony-stimulating factor and functional outcome after ischemic stroke: an observational study.

Objectives: While granulocyte colony-stimulating factor (G-CSF) has shown beneficial effects in experimental ischemic stroke (IS), these effects have not been reproduced clinically. Small-to-medium-sized observational studies have reported varying associations for G-CSF with stroke severity and post-stroke functional outcome, prompting their investigation in a larger study.Methods: Endogenous serum G-CSF (S-GCSF) was measured in the acute phase and after 3 months in patients with IS (N = 435; 36% females; mean age, 57 years) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was scored according to the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) assessed functional outcomes at 3-month and 2-year post-stroke. Correlation and logistic regression analyses with confounder adjustments assessed the relationships.Results: The acute S-GCSF level was 23% higher than at 3-month post-stroke (p < 0.001). Acute G-CSF correlated weakly with stroke severity quintiles (r = 0.12, p = 0.013) and with high-sensitivity C-reactive protein (r = 0.29, p < 0.001). The association between S-GCSF (as quintiles, q) and poor functional outcome at 3 months (mRS 3-6; S-GCSF-q5 vs. S-GCSF-q1, age- and sex-adjusted odds ratio: 4.27, 95% confidence interval: 1.82-9.99; p = 0.001) withstood adjustment for cardiovascular risk factors and stroke subtype, but not additional correction for stroke severity. Post-stroke changes in S-GSCF and absolute 3-month S-GCSF were not associated with 3-month or 2-year functional outcomes.Discussion: Early post-stroke S-GCSF is increased in severe IS and associated with 3-month poor functional outcomes. The change in S-GCSF and the 3-month S-GCSF appear to be less-important, and S-GCSF likely reflects inflammation in large infarctions.

Circulating levels of vascular endothelial growth factor and post-stroke long-term functional outcome.

OBJECTIVES: Vascular endothelial growth factor (VEGF) acts in angiogenesis and neuroprotection, although the beneficial effects on experimental ischemic stroke (IS) have not been replicated in clinical studies. We investigated serum VEGF (s-VEGF) in the acute stage (baseline) and 3 months post-stroke in relation to stroke severity and functional outcome. METHODS: The s-VEGF and serum high-sensitivity C-reactive protein (hs-CRP) concentrations were measured in patients enrolled in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) at the acute time-point (median 4 days, N = 492, 36% female; mean age, 57 years) and at 3 months post-stroke (N = 469). Baseline stroke severity was classified according to the National Institutes of Health Stroke Scale (NIHSS), and functional outcomes (3 months and 2 years) were evaluated using the modified Rankin Scale (mRS), dichotomized into good (mRS 0-2), and poor (mRS 3-6) outcomes. Multivariable logistic regression analyses were adjusted for covariates. RESULTS: The baseline s-VEGF did not correlate with stroke severity but correlated moderately with hs-CRP (r = .17, P < .001). The baseline s-VEGF was 39.8% higher in total anterior cerebral infarctions than in lacunar cerebral infarctions. In binary logistic regression analysis, associations with 3-month functional outcome were non-significant. However, an association between the 3-month s-VEGF and poor 2-year outcome withstood adjustments for age, sex, cardiovascular covariates, and stroke severity (per 10-fold increase in s-VEGF, odds ratio [OR], 2.56, 95% confidence interval [CI] 1.12-5.82) or hs-CRP (OR 2.53, CI 1.15-5.55). CONCLUSIONS: High 3-month s-VEGF is independently associated with poor 2-year functional outcome but not with 3-month outcome.