Elsevier

American Heart Journal

Volume 154, Issue 4, October 2007, Pages 736-742
American Heart Journal

Clinical Investigations
Acute Ischemic Heart Disease
C-terminal pro–endothelin-1 offers additional prognostic information in patients after acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) Study

https://doi.org/10.1016/j.ahj.2007.06.016Get rights and content

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 pro–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 to 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). C-terminal pro–endothelin-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 < .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, sex, history of AMI, and therapy with β-blockers). The areas under the receiver operating curve 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 end points.

Conclusion

The endothelin system is known to be activated post AMI. C-terminal pro–endothelin-1 is a powerful predictor of adverse outcome, along with NTproBNP. CT-proET-1 may represent a clinically useful marker of prognosis after AMI.

Section snippets

Study population

We studied 983 consecutive AMI patients admitted to the Coronary Care Unit of Leicester Royal Infirmary. The study complied with the Declaration of Helsinki and was approved by the local ethics committee; written informed consent was obtained from patients. AMI was diagnosed if a patient had a plasma creatine kinase–MB elevation greater than twice normal or cardiac troponin I level >0.1 ng/mL with at least 1 of the following: chest pain lasting >20 minutes or diagnostic serial

Patient characteristics

The demographic features of the patient population are shown in Table I. Median range of follow-up was 343 days ranging from 0 to 764 days. No patient was lost to follow-up, and the minimum length of follow-up for survivors was 60 days, enabling a censored primary end point of death or HF to be determined at this time point for ROC analysis. During follow-up, 101 patients (10.3%) died, and 49 (5.0%) were readmitted with HF. In 783 patients, the AMI was a STEMI event.

Plasma profile of CT-proET-1 and NTproBNP

Daily blood samples were

Discussion

We have shown, using survival analysis, that CT-proET-1 is a powerful independent predictor of death and HF, with combined levels of CT-proET-1 and NTproBNP performing better at identifying patients with the highest risk for an adverse event than either marker alone. The prognostic ability of CT-proET-1 at predicting death or HF is independent of well-established clinical and biochemical factors including the well-established NTproBNP. This has been borne out in the multivariate analyses with

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  • Cited by (0)

    Conflicts of interest: A Bergmann holds ownership in BRAHMS AG, patent rights to the markers of the study and is a member of the board of directors of BRAHMS AG. J Struck holds patent rights to the markers and is an employee of BRAHMS AG. N Morgenthaler is an employee of BRAHMS AG. BRAHMS is a mid-sized company, based in Hennigsdorf, Germany, commercializes immunoassays, and has developed the CT-proET-1 assay, for which it owns patent rights.

    Dr Sohail Q. Khan is supported by a British Heart Foundation Junior Research Fellowship (FS/03/028/15486). This study was not financed by BRAHMS AG.

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