Plasma midregional pro-adrenomedullin improves prediction of functional outcome in ischemic stroke

T Seifert-Held,T Pekar,T Gattringer,N.E Simmet,H Scharnagl,C Bocksrucker,C Lampl,M.K Storch,T Stojakovic,F Fazekas

doi:10.1016/j.jns.2013.07.709

Abstract

Background: To evaluate if plasma levels of midregional pro-adrenomedullin (MR-proADM) improve prediction of functional outcome in ischemic stroke. Methods: In 168 consecutive ischemic stroke patients, plasma levels of MR-proADM were measured within 24 hours from symptom onset. Functional outcome was assessed by the modified Rankin Scale (mRS) at 90 days following stroke. Logistic regression, receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), and Kaplan-Meier survival analysis were applied. Results: Plasma MR-proADM levels were found significantly higher in patients with unfavourable (mRS 3–6) compared to favourable (mRS 0–2) outcomes. MR-proADM levels were entered into a predictive model including the patients’ age, National Institutes of Health Stroke Scale (NIHSS), and the use of recanalization therapy. The area under the ROC curve did not increase significantly. However, category-free NRI of 0.577 (p,0.001) indicated a significant improvement in reclassification of patients. Furthermore, MR-proADM levels significantly improved reclassification of patients in the prediction of outcome by the Stroke Prognostication using Age and NIHSS-100 (SPAN-100; NRI=0.175; p=0.04). KaplanMeier survival analysis showed a rising risk of death with increasing MR-proADM quintiles. Conclusions: Plasma MR-proADM levels improve prediction of functional outcome in ischemic stroke when added to the patients’ age, NIHSS on admission, and the use of recanalization therapy. Levels of MR-proADM in peripheral blood improve reclassification of patients when the SPAN-100 is used to predict the patients’ functional outcome.

Highlights

Ischemic stroke is among the leading causes of death and disability and utilises a huge amount of health care expenses
[3] Several proteins in peripheral blood which are related to an acute stress response have recently been shown to improve outcome prediction in ischemic stroke. [4,5,6,7] As derived from observations in patients with myocardial infarction and congestive heart failure (CHF), plasma midregional pro-adrenomedullin (MR-proADM) is an independent predictor of death. [8,9] We hypothesized that MR-proADM
[14] Adrenomedullin is difficult to measure in peripheral blood because of complex formation and rapid clearance from the circulation. [15,16] The more stable MR-proADM is secreted in equimolar amounts to adrenomedullin and can be reliably detected in human plasma. [17,18]

Summary

Introduction

Ischemic stroke is among the leading causes of death and disability and utilises a huge amount of health care expenses. Clinical criteria which predict worse functional outcome include increased age and higher National Institutes of Health Stroke Scale (NIHSS) on admission. [3] Several proteins in peripheral blood which are related to an acute stress response have recently been shown to improve outcome prediction in ischemic stroke. [4,5,6,7] As derived from observations in patients with myocardial infarction and congestive heart failure (CHF), plasma midregional pro-adrenomedullin (MR-proADM) is an independent predictor of death. [8,9] We hypothesized that MR-proADM would reflect the acute stress response in ischemic stroke and could be used to predict functional outcome. To evaluate if plasma levels of midregional pro-adrenomedullin (MR-proADM) improve prediction of functional outcome in ischemic stroke

Methods

Results

Conclusion