Growth differentiation factor-15 predicts poor survival after cardiac arrest

Background: Early prognostication in post-cardiac arrest (CA) patients remains challenging and biomarkers have evolved as helpful tools in risk assessment. The stress-response cytokine growth differentiation factor-15 (GDF-15) is dramatically up-regulated during various kinds of tissue injury and predicts outcome in many pathological conditions. We aimed to assess the predictive value of circulating GDF-15 in post-CA patients.

Methods: This prospective observational study included 128 consecutive patients (median age 60.3 years, 75.8% male) with return of spontaneous circulation after in- or out-of-hospital CA who were treated at a tertiary university hospital. GDF-15 serum levels were determined at admission.

Results: A total of 52 patients (40.6%) died during the 6-month follow-up. Median GDF-15 levels were significantly lower in survivors (1601 ng/L (interquartile range: 1114-2983 ng/L) than in non-survivors (3172 ng/L (1927-8340 ng/L); p < 0.001). GDF-15 levels were also significantly lower in patients with favourable neurological 6-month outcome (cerebral performance category (CPC) 1-2) than in those with poor neurological outcome (CPC 3-5; p < 0.001). GDF-15 significantly predicted 6-month mortality in univariate Cox regression analysis (hazard ratio (HR) per 1-standard deviation increase 1.76 [95% confidence interval (CI) 1.35-2.31; p < 0.001] and remained significant after multivariable adjustment (HR 1.57 [95% CI 1.19-2.07; p = 0.001]). Subgroup analysis revealed that the association between GDF-15 and 6-month outcome was present both in patients with in- and out-of-hospital CA.

Conclusions: GDF-15 predicts poor survival and neurological outcome in post-CA patients. GDF-15 may reflect the extent of hypoxic injury to the brain and other organs and might help to improve early risk stratification after CA.