C-terminal pro-endothelin-1 offers additional prognostic information in patients after acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) Study.
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 beta-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.


CONCLUSIONS
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.
Khan
Sohail Q
SQ
Department of Cardiovascular Sciences, University of Leicester, Leicester Royal Infirmary, Leicester, UK. sqk1@le.ac.uk <sqk1@le.ac.uk>
Dhillon
Onkar
O
Struck
Joachim
J
Quinn
Paulene
P
Morgenthaler
Nils G
NG
Squire
Ian B
IB
Davies
Joan E
JE
Bergmann
Andreas
A
Ng
Leong L
LL
D000368:Aged; D015897:Comorbidity; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology / Q000401:mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011498:Protein Precursors / Q000097:blood*; D012372:ROC Curve; D018570:Risk Assessment; D016019:Survival Analysis
C557077:C-terminal proendothelin-1; D019332:Endothelin-1; D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); C093240:proendothelin 1; D020097:Natriuretic Peptide, Brain