AUTHOR=Westphal Laura P. , Schweizer Juliane , Fluri Felix , De Marchis Gian Marco , Christ-Crain Mirjam , Luft Andreas R. , Katan Mira 

TITLE=C-Terminal-Pro-Endothelin-1 Adds Incremental Prognostic Value for Risk Stratification After Ischemic Stroke

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.629151

DOI=10.3389/fneur.2020.629151

ISSN=1664-2295

ABSTRACT=<p><bold>Background and Aims:</bold> Endothelins have shown to play a role in the pathophysiology of ischemic stroke. We aimed at evaluating the incremental prognostic value of C-terminal-pro-endothelin-1 (CT-pro-ET-1) in a well-described cohort of acute stroke patients.</p><p><bold>Methods:</bold> We performed serial measurements of CT-pro-ET-1 in 361 consecutively enrolled ischemic stroke patients and assessed functional outcome and mortality after 90 days. As we found peak levels of CT-pro-ET-1 and the most prominent association with mortality on day 1 after admission (<italic>n</italic> = 312), we focused on this time point for further outcome analyses. We calculated logistic regression and cox proportional hazards models to estimate the association of CT-pro-ET-1 with our outcome measures after adjusting for demographic and clinical risk factors. To evaluate the incremental value of CT-pro-ET-1, we calculated the area under the receiver operating characteristics (AUC) curve and the continuous net reclassification index (cNRI) comparing the model with and without the biomarker CT-pro-ET-1.</p><p><bold>Results:</bold> In the univariate analysis CT-pro-ET-1 with a peak on day 1 after admission was associated with unfavorable outcome with an OR of 1.32 (95% CI, 1.16–1.51, <italic>p</italic> &lt; 0.001) and with mortality with a HR of 1.45 (95% CI, 1.29–1.63, <italic>p</italic> &lt; 0.001). After adjusting, CT-pro-ET-1 remained an independent predictor of mortality with an adjusted HR of 1.50 (95% CI, 1.29–1.74, <italic>p</italic> &lt; 0.001), but not for functional outcome. Adding CT-pro-ET-1 to the cox-regression model for mortality, the discriminatory accuracy improved from 0.89 (95% CI, 0.84–0.94) to 0.92 (95% CI, 0.88–0.96) <italic>p</italic> &lt; 0.001, and the cNRI was 0.72 (95% CI, 0.17–1.13).</p><p><bold>Conclusion:</bold> CT-pro-ET-1 with a peak level on day 1 was an independent predictor of mortality adding incremental prognostic value beyond traditional risk factors.</p>