This is the authors' final draft of the paper published as American Heart Journal, 2007, 154(4), pp.736-742. The final published version is available on Science Direct, doi:10.1016/j.ahj.2007.06.016.Background: Endothelin-1 is elevated in heart failure (HF) and after acute myocardial infarction (AMI) and gives prognostic information on mortality. Another part of its precursor, C-terminal Pro-Endothelin-1 (CT-proET-1), is more stable in circulation and ex-vivo. We investigated the cardiovascular prognostic value post-AMI of CT-proET-1 and compared it to N-terminal B-type natriuretic peptide (NTproBNP), a marker of death and HF. Methods: We measured plasma CT-proET-1 and NTproBNP in 983 consecutive post-AMI patients (721 men, mean age 65.0±(SD)12.2 years), 3-5 days after chest pain onset. Results: There were 101 deaths and 49 readmissions with HF during follow up (median 343, range 0-764 days). CT-proET-1 was raised in patients with death or HF compared to survivors (median [range]pmol/L, 119.0[14.0-671.0] vs. 73.0[4.6-431.0]; p<0.0001). Using a Cox proportional hazards logistic model, log CT-proET-1 (HR 6.82) and log NTproBNP (HR 2.62) were significant independent predictors of death or HF (along with age, gender, past history of AMI and therapy with beta blockers). The areas under the receiver-operating curve (AUC) for CT-proET-1, NTproBNP and the logistic model with both markers were 0.76, 0.76 and 0.81 respectively. Findings were similar for death and HF as individual endpoints. Conclusion: The endothelin system is known to be activated post-AMI. CT-proET-1 is a powerful predictor of adverse outcome along with NTproBNP. CT-proET-1 may represent a clinically useful marker of prognosis after AMI
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