Utility of C-terminal proendothelin in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction.
BACKGROUND
Endothelial dysfunction plays a major role in cardiovascular diseases, including acute myocardial infarction (AMI). However, its quantification has not been available as a clinical tool.


METHODS
In a prospective international multicentre study, we analyzed the diagnostic and prognostic utility of endothelial dysfunction as quantified by C-terminal proendothelin-1 (CT-proET-1) in 658 consecutive patients presenting with suspected AMI. The final diagnosis was adjudicated by 2 independent cardiologists. Patients were followed long-term for mortality.


RESULTS
The adjudicated final diagnosis was AMI in 145 patients (22%). The diagnostic performance of CT-proET-1 for AMI was moderate; its area under the receiver operating characteristic (ROC) curve amounted to 0.66 (95% confidence interval [CI], 0.61-0.72; P < 0.001). There was no significant increase in the AUC when CT-proET-1 was added to either cardiac troponin T (cTnT) or high-sensitivity cTnT (hs-cTnT). Seventy four percent of patients who died during the first 24 months (n = 50) were in the fourth quartile of the CT-proET-1 presentation value (>82 pmol/L). The prognostic accuracy of CT-proET-1 regarding mortality was tantamount to that of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and outperformed cTnT and hs-cTnT both in patients with AMI and in patients without acute coronary syndrome. CT-proET-1 at presentation yielded high prognostic accuracy that was similar to that of the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores. The TIMI risk score could be significantly improved by adding CT-proET-1 (integrated discriminatory improvement [IDI] of 0.074 P = 0.004).


CONCLUSIONS
Use of CT-proET-1 improves risk stratification of unselected patients with suspected AMI. CT-proET-1 did not provide additional diagnostic value.
Department of Internal Medicine, University Hospital, Basel, Switzerland; Department of Cardiology, University Hospital, Basel, Switzerland.
Philip
P
Haaf
Department of Internal Medicine, University Hospital, Basel, Switzerland.
Christa
C
Zellweger
Department of Cardiology, Brigham & Women's Hospital, Boston, Massachusetts, USA.
Tobias
T
Reichlin
Department of Internal Medicine, University Hospital, Basel, Switzerland; Department of Cardiology, University Hospital, Basel, Switzerland.
Anina
A
Zbinden
Department of Internal Medicine, University Hospital, Basel, Switzerland; Department of Cardiology, University Hospital, Basel, Switzerland.
Karin
K
Wildi
Department of Internal Medicine, University Hospital, Basel, Switzerland; Department of Cardiology, University Hospital, Basel, Switzerland.
Tamina
T
Mosimann
Department of Internal Medicine, University Hospital, Basel, Switzerland; Department of Cardiology, University Hospital, Basel, Switzerland.
Raphael
R
Twerenbold
Department of Internal Medicine, University Hospital, Basel, Switzerland; Department of Cardiology, University Hospital, Basel, Switzerland.
Miriam
M
Reiter
Department of Internal Medicine, University Hospital, Basel, Switzerland; Department of Cardiology, University Hospital, Basel, Switzerland.
Cathrin
C
Balmelli
Department of Laboratory Medicine, University Hospital, Basel, Switzerland.
Heike
H
Freidank
Servicio de Pneumologia, Hospital del Mar - IMIM, UPF, CIBERES, ISC III, Barcelona, Spain; Servicio de Urgencias, Hospital del Mar - IMIM, Barcelona, Spain.
Maria Rubini
MR
Gimenez
Servicio de Pneumologia, Hospital del Mar - IMIM, UPF, CIBERES, ISC III, Barcelona, Spain; Servicio de Urgencias, Hospital del Mar - IMIM, Barcelona, Spain.
Federico
F
Peter
Department of Cardiology, University Hospital, Basel, Switzerland.
Michael
M
Freese
Department of Cardiology, University Hospital, Basel, Switzerland.
Claudia
C
Stelzig
Department of Internal Medicine, University Hospital, Basel, Switzerland.
Beate
B
Hartmann
Research Department, BRAHMS GmbH, Thermo Fisher Scientific, Henningsdorf, Germany.
Christiane
C
Dinter
Department of Cardiology, University Hospital, Basel, Switzerland.
Stefan
S
Osswald
Department of Cardiology, University Hospital, Basel, Switzerland. Electronic address: christian.mueller@usb.ch.
Christian
C
Mueller
D000368:Aged; D042241:Early Diagnosis; D004562:Electrocardiography; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013557:Switzerland / Q000453:epidemiology
C557077:C-terminal proendothelin-1; D019332:Endothelin-1; D010446:Peptide Fragments