Abstract
IntroductionThere is no single blood marker for predicting the prognosis in ischemic stroke. A combination of multiple blood markers may enhance the ability to predict long-term outcome following ischemic stroke.MethodsBlood concentrations of neuronal markers (neuron-specific enolase, visinin-like protein 1, heart type fatty acid binding protein (hFABP) and neuroglobin), astroglial markers (S100B and glial fibrillary acidic protein), inflammatory markers (IL-6, TNF-α, and C-reactive protein), blood-brain barrier marker (matrix metalloproteinase 9), and haemostatic markers (D-dimer and PAI-1) were measured within 24 hours after stroke onset. The discrimination and reclassification for favorable and poor outcome were compared after adding individual or a combination of blood markers to the clinical model of stroke outcome.ResultsIn multivariate analysis, natural log-transformed (log) IL-6 (odds ratio (OR): 1.75, 95% CI: 1.25 to 2.25, P = 0.001) and loghFABP (OR: 3.23, 95% CI: 1.44 to 7.27, P = 0.005) were independently associated with poor outcome. The addition of a single blood marker to the clinical model did not improve the discriminating ability of the clinical model of stroke outcome. However, the addition of the combination of logIL-6 and loghFABP to the clinical model showed improved discrimination (area under receiver operating characteristic (AUROC) curve: 0.939 versus 0.910, P = 0.03) and reclassification performance (net reclassification improvement index: 0.18, P = 0.005).ConclusionsA combination of circulating IL-6 and hFABP level has an additive clinical value for the prediction of stroke outcome.
Highlights
There is no single blood marker for predicting the prognosis in ischemic stroke
The univariate logistic regression model indicates that age (OR: 1.58, 95% CI: 1.17 to 2.12, P = 0.002), initial National Institutes of Health Stroke Scale (NIHSS) score (OR: 4.20, 95% CI: 2.70 to 6.52, P < 0.001), atrial fibrillation (Afib) (OR: 4.29, 95% CI: 2.17 to 8.48, P < 0.001) and white blood cells (WBC) count (adjusted odds ratio (OR): 1.11, 95% CI: 1.03 to 1.19, P = 0.005) were associated with poor prognosis
In the multivariate analysis of clinical variables, only age and initial NIHSS showed a strong association with poor stroke outcome, with the disappearance of significance for Afib and WBC count (P > 0.05)
Summary
There is no single blood marker for predicting the prognosis in ischemic stroke. A combination of multiple blood markers may enhance the ability to predict long-term outcome following ischemic stroke. Blood markers of neuronal injury, astroglial injury, inflammatory mediators, and/or thrombotic/haemostatic proteins are candidate blood markers for early stroke recurrence or long-term clinical outcome in previous case-control studies [7,8,9,10,11]. For the clinical application of biomarkers for stroke prognosis, candidate blood markers must satisfy the proposed criteria for an ideal blood marker [4,12]; 1) the marker has a statistically independent association with outcome after adjusting for clinical covariates; 2) the marker improves the discriminating ability of the established clinical model; and 3) the marker can reclassify patients at low or high risk for poor outcome across clinically relevant thresholds of predicted probabilities of stroke outcome. Clinically applicable panels of blood markers should be evaluated in subsequent studies
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