Association of serum growth differentiation factor-15 levels with the risks of death and vascular events in patients with ischemic stroke: The role of diabetes

Background and aims: Researchers have not determined whether the association between growth differentiation factor-15 (GDF-15) levels and stroke outcomes is modified by the diabetes status. We aimed to evaluate the prognostic value of GDF-15 among patients with ischemic stroke stratified by diabetes.

Methods and results: A total of 3001 patients with ischemic stroke were selected from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) and included in this study. The primary outcome was a composite outcome of death and vascular events at 3 months after acute ischemic stroke. An elevated GDF-15 level was significantly associated with the primary outcome in patients with diabetes but not in those without diabetes (p_interaction = 0.038). The multivariate-adjusted hazard ratio (95% confidence intervals) for the primary outcome was 3.33 (1.07-10.35) when 2 extreme tertiles were compared, and a linear association between GDF-15 levels and the primary outcome was observed in patients with diabetes (p for linearity = 0.046). The addition of serum GDF-15 to conventional risk factors improved the risk prediction for the primary outcome in patients with diabetes (net reclassification improvement: 31.98%, p = 0.043; integrated discrimination index: 0.85%, p = 0.034) but not in those without diabetes.

Conclusions: A modifying effect of the diabetes status on the association between serum GDF-15 levels and ischemic stroke prognosis was observed. Elevated serum GDF-15 levels were associated with the primary outcome within 3 months after ischemic stroke in patients with diabetes, suggesting that GDF-15 may be an important prognostic factor for ischemic stroke in patients with diabetes.