A prospective cohort study on decreased serum apelin-13 levels after human aneurysmal subarachnoid hemorrhage: associations with severity and prognosis

Apelin-13 may have neuroprotective effects. We aimed to determine whether serum apelin-13 could serve as a potential biomarker for severity, delayed cerebral ischemia (DCI), and prognosis after human aneurysmal subarachnoid hemorrhage (aSAH). In this prospective, observational, cohort, single-center study of 139 patients with aSAH and 139 healthy individuals, serum apelin-13 levels were determined. The indicators of stroke severity were the Hunt-Hess scale and the modified Fisher grading scale. The prognostic parameters were DCI and 6-month worse prognosis (Extended Glasgow Outcome Scale scores of 1–4). Using binary logistic regression analysis, the relationship between serum apelin-13 levels and prognosis was reported as odds ratios (ORs) with 95% confidence intervals (CIs). Under the receiver operating characteristic curve, prognostic abilities were shown as areas under the curve (AUCs) with 95% CIs. Serum apelin-13 levels were substantially lower in patients than in controls (median, 28.8 versus 48.6 ng/ml; P < 0.001), in patients with DCI than in non-DCI patients (median, 14.9 versus 31.6 ng/ml; P < 0.001), and in patients with worse prognosis than in those with good prognosis (median, 16.3 versus 33.7 ng/ml; P < 0.001). Serum apelin-13 levels were independently correlated with Hunt-Hess scores (beta, -6.836; 95% CI, -8.963–4.708; VIF, 2.219; P = 0.001) and modified Fisher scores (beta, -3.350; 95% CI, -6.151–0.549; VIF, 1.562; P = 0.019). Serum apelin-13 levels were an independent predictor of DCI (OR, 0.951; 95% CI, 0.914–0.990; P = 0.022) and worse prognosis (OR, 0.954; 95% CI, 0.916–0.993; P = 0.013). Serum apelin-13 levels significantly differentiated DCI and poor prognosis, with AUCs of 0.753 (95% CI, 0.656–0.850) and 0.791 (95% CI, 0.713–0.868) respectively. Using the Youden method, serum apelin-13 levels < 19.3 ng/ml distinguished the risk of DCI with 64.7% sensitivity and 77.1% specificity, and serum apelin-13 levels < 30.2 ng/ml discriminated the development of worse prognosis with 89.1% sensitivity and 63.4% specificity. Serum apelin-13 levels combined with Hunt-Hess scores and modified Fisher scores displayed a significantly higher AUC than any one of them for prognostic prediction (all P < 0.05). Decreased serum apelin-13 levels, which are strongly correlated with disease severity, independently predicted poor outcomes following aSAH, substantializing serum apelin-13 as a useful prognostic biomarker of aSAH.