Objective: Endothelins have shown to play a role in ischemic stroke pathophysiology. However, only controversial data in mainly small studies exist. We aimed at evaluating the incremental prognostic value of endothelin-1 in a well-described cohort of acute stroke patients.

Methods: In this prospective cohort-study we prospectively measured endothelin-1 levels of 362 ischemic stroke patients within 72h of symptoms onset.  Outcome measures were functional outcome (defined as a modified Rankin Scale of ≤2 for good and ≥3 for unfavourable outcome) and mortality after 90 days. We calculated logistic regression and cox proportional hazards models, respectively, to estimate the association of endothelin-1 with our outcome measures after adjusting for demographic and medical risk factors. To assess the discriminatory accuracy and the incremental value of endothelin-1 beyond known risk factors, we calculated and compared the area under the receiver operating characteristics (AUC) curve. 

Results: In the univariate analysis endothelin-1 was associated with unfavourable outcome with an OR of 1.32 [95% CI, 1.16 – 1.51] and with mortality with a HR of 1.45  [95% CI, 1.29 – 1.63]. After adjusting, endothelin-1 remained an independent predictor for mortality with an adjusted HR of 1.58  [95% CI, 1.34 – 1.85] but not for functional outcome. Adding endothelin-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. The addition of ET-1 to the multivariate model for mortality led to a continous NRI of 0.76 [95%CI, 0.32–1.15].

Conclusion: Endothelin-1 was an independent predictor of mortality adding incremental prognostic value beyond traditional demographic and vascular risk factors.  These results need further validation in independent larger cohorts.

THE ROLE OF C-TERMINAL-PRO-ENDOTHELIN-1 IN PREDICTING ISCHEMIC STROKE OUTCOME