Plasma Growth Differentiation Factor − 8 / Myostatin Level As Prognostic Biomarker of Patients with Ischemic Stroke and Acute Revascularization Therapy. PARADISE Study

Background: Identifying biological markers of ischemic stroke (IS) is an important research approach to develop innovative therapeutic strategies. This study aimed to assess the association between plasma Growth Differentiation Factor-8 (GDF-8)/Myostatin levels and outcome of IS patients.Methods: Consecutive patients with acute IS treated with either intravenous thrombolysis and/or mechanical thrombectomy at Dijon University Hospital, France were prospectively included. Clinical variables were recorded, and plasma GDF-8 was collected just after the revascularization procedure. Primary endpoint was functional outcome at 3 months assessed by the modified Rankin Scale (mRS) score. Secondary endpoints included mRS scores at 6 and 12 months, and overall mortality over 1-year of follow-up.Results: Among the 173 included patients (median age: 76 years, Interquartile range (IQR): 66-85; 49% women), median plasma GDF-8 levels at admission were significantly lower in those with a poor outcome at 3 months defined as a mRS score > 2 (2073 (IQR: 1564-2757) pg/mL versus 1471 (1192-2241) pg/mL, p < 0.001). Lower GDF-8 levels at admission were associated with higher 3-months mRS score in multivariable ordinal logistic regression analysis (OR = 0.9995; 95% CI: 0.9991-0.9999, p = 0.011). The association was also observed with 6and 12-month mRS scores. Although mortality was higher in patients with lower GDF-8 levels, the association was not significant in multivariable Cox analysis.Conclusion: Lower plasma GDF-8 levels were associated with a poorer functional outcome in IS patients treated with acute revascularization therapy. Underlying pathophysiological mechanisms involving GDF-8 in post-stroke outcome remain to be elucidated.