Serum Soluble Scavenger Receptor A Levels are Associated with Delayed Cerebral Ischemia and Poor Clinical Outcome After Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Study

Abstract

Objective: Scavenger receptor A (SRA), a pattern recognition molecule, is implicated in immune response after acute brain injury. We strived to identify serum soluble SRA (sSRA) as a potential biomarker of prognosis after aneurysmal subarachnoid hemorrhage (aSAH).

Methods: In this prospective observational study, we quantified serum sSRA levels of 131 aSAH patients and 131 healthy controls. A poor outcome was defined as extended Glasgow outcome scale (GOSE) scores of 1-4 at 90 days after injury. Relations of serum sSRA levels to severity, delayed cerebral ischemia (DCI) and poor outcome were assessed using multivariate analysis. Predictive efficiency was determined via area under receiver operating characteristic curve (AUC).

Results: Serum sSRA levels were markedly higher in aSAH patients than in controls (median, 2.9 ng/mL versus 1.0 ng/mL; P < 0.001). Serum sSRA levels were independently correlated with Hunt-Hess scores (beta, 0.569; 95% confidence interval (CI), 0.244-0.894; P = 0.001), modified Fisher scores (beta, 0.664; 95% CI, 0.254-1.074; P = 0.002) and 90-day GOSE scores (beta, -0.275; 95% CI, -0.440-0.110; P = 0.005). Serum sSRA levels independently predicted DCI (odds ratio, 1.305; 95% CI, 1.012-1.687; P = 0.040) and a poor outcome (odds ratio, 2.444; 95% CI, 1.264-4.726; P = 0.008), as well as showed significant accuracy for the discrimination of DCI (AUC, 0.753; 95% CI, 0.649-0.857; P < 0.001) and a poor outcome (AUC, 0.800; 95% CI, 0.721-0.880; P < 0.001). Its combination with Hunt-Hess scores and modified Fisher scores displayed significantly improved AUCs for predicting DCI and poor outcome, as compared to any of them (all P < 0.05).

Conclusion: There is a significant elevation of serum sSRA levels after aSAH, which in close correlation with illness severity, are independently associated with DCI and poor clinical outcome after aSAH. Hypothetically, SRA may regulate immune response in acute brain injury after aSAH and serum sSRA is presumed to be a potential prognostic biomarker of aSAH.

Keywords: aneurysm; biomarkers; delayed cerebral ischemia; mechanism; prognosis; scavenger receptor A; severity; subarachnoid hemorrhage.

Figure 1

Flowing-chart for choosing eligible patients with aneurysmal subarachnoid hemorrhage. A total of 187 patients with aneurysmal subarachnoid hemorrhage were initially recruited during the study period and afterwards 179 patients were retained for further analysis based on the inclusion criteria. Next, 48 patients were excluded because of the exclusion criteria and finally 131 patients were assessed for clinical investigation.

Figure 2

Differences in terms of serum soluble scavenger receptor A levels between healthy controls and patients with aneurysmal subarachnoid hemorrhage. Patients had significantly higher serum soluble scavenger receptor A levels than healthy controls (P<0.001). sSRA indicates soluble scavenger receptor A.

Figure 3

Relationship between serum soluble scavenger receptor A levels and hemorrhagic severity after aneurysmal subarachnoid hemorrhage. (A) Relationship between serum soluble scavenger receptor A levels and modified Fisher scores following aneurysmal subarachnoid hemorrhage. (B) Relationship between serum soluble scavenger receptor A levels and Hunt-Hess scores following aneurysmal subarachnoid hemorrhage. Serum soluble scavenger receptor A levels were substantially highest in patients with modified Fisher score 4 or Hunt-Hess score 5, followed by modified Fisher scores 2 and 3, or Hunt-Hess scores 2, 3 and 4, and were significantly lowest in those with modified Fisher score 1 or Hunt-Hess score 1 (both P<0.001). sSRA indicates soluble scavenger receptor A.

Figure 4

Discriminatory ability of serum soluble scavenger receptor A levels for the risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Serum soluble scavenger receptor A levels substantially distinguished patients with the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (P<0.001). Using Youden method, a suitable value was selected, which generated the corresponding sensitivity and specificity values in DCI prediction. DCI means delayed cerebral ischemia.

Figure 5

Relationship between serum soluble scavenger receptor A levels and extended Glasgow outcome scale scores after aneurysmal subarachnoid hemorrhage. Serum soluble scavenger receptor A levels were substantially highest in patients with extended Glasgow outcome scale score 1, followed by scores 2–7, were significantly lowest in those with extended Glasgow outcome scale score 8 (P<0.001). sSRA indicates soluble scavenger receptor A. GOSE denotes extended Glasgow outcome scale.

Figure 6

Serum soluble scavenger receptor A levels with respect to distinguishable capability for patients at risk of a poor outcome at 90 days following aneurysmal subarachnoid hemorrhage. A poor outcome was defined as extended Glasgow outcome scale scores of 1–4 at 90 days after stroke. Serum soluble scavenger receptor A levels substantially differentiated between patients with a poor outcome and those without a poor outcome after aneurysmal subarachnoid hemorrhage (P<0.001). Using Youden method, an optimal value was chosen, which yielded the corresponding sensitivity and specificity values in prognostic prediction.