CRP (C-Reactive Protein) in Outcome Prediction After Subarachnoid Hemorrhage and the Role of Machine Learning

Abstract

Outcome prediction after aneurysmal subarachnoid hemorrhage (aSAH) is challenging. CRP (C-reactive protein) has been reported to be associated with outcome, but it is unclear if this is independent of other predictors and applies to aSAH of all grades. Therefore, the role of CRP in aSAH outcome prediction models is unknown. The purpose of this study is to assess if CRP is an independent predictor of outcome after aSAH, develop new prognostic models incorporating CRP, and test whether these can be improved by application of machine learning. This was an individual patient-level analysis of data from patients within 72 hours of aSAH from 2 prior studies. A panel of statistical learning methods including logistic regression, random forest, and support vector machines were used to assess the relationship between CRP and modified Rankin Scale. Models were compared with the full Subarachnoid Hemmorhage International Trialists’ (SAHIT) prediction tool of outcome after aSAH and internally validated using cross-validation. One thousand and seventeen patients were included for analysis. CRP on the first day after ictus was an independent predictor of outcome. The full SAHIT model achieved an area under the receiver operator characteristics curve (AUC) of 0.831. Addition of CRP to the predictors of the full SAHIT model improved model performance (AUC, 0.846, P=0.01). This improvement was not enhanced when learning was performed using a random forest (AUC, 0.807), but was with a support vector machine (AUC of 0.960, P <0.001). CRP is an independent predictor of outcome after aSAH. Its inclusion in prognostic models improves performance, although the magnitude of improvement is probably insufficient to be relevant clinically on an individual patient level, and of more relevance in research. Greater improvements in model performance are seen with support vector machines but these models have the highest classification error rate on internal validation and require external validation and calibration.