Laura P Westphal1, Juliane Schweizer1, Felix Fluri2, Gian Marco De Marchis3, Mirjam Christ-Crain4, Andreas R Luft1, Mira Katan1. 1. Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland. 2. Department of Neurology, Stiftung Rehabilitation Heidelberg (SRH) Health Center Bad Wimpfen, Bad Wimpfen, Germany. 3. Department of Neurology, University Hospital Basel and University of Basel, Basel, Switzerland. 4. Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel and University of Basel, Basel, Switzerland.
Abstract
Background and Aims: 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. Methods: 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 (n = 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. Results: 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, p < 0.001) and with mortality with a HR of 1.45 (95% CI, 1.29-1.63, p < 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, p < 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) p < 0.001, and the cNRI was 0.72 (95% CI, 0.17-1.13). Conclusion: 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.
Background and Aims: 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 strokepatients. Methods: We performed serial measurements of CT-pro-ET-1 in 361 consecutively enrolled ischemic strokepatients 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 (n = 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. Results: 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, p < 0.001) and with mortality with a HR of 1.45 (95% CI, 1.29-1.63, p < 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, p < 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) p < 0.001, and the cNRI was 0.72 (95% CI, 0.17-1.13). Conclusion: 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.
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