Published Online
on April 9, 2007

A more recent version of this article appeared on April 24, 2007

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Submitted on July 28, 2006
Accepted on February 16, 2007

C-Terminal Provasopressin (Copeptin) as a Novel and Prognostic Marker in Acute Myocardial Infarction. Leicester Acute Myocardial Infarction Peptide (LAMP) Study

Sohail Q. Khan MB, Onkar S. Dhillon MB, Russell J. O’Brien MB, Joachim Struck PhD, Paulene A. Quinn MPhil, Nils G. Morgenthaler PhD, Iain B. Squire MD, Joan E. Davies PhD, Andreas Bergmann PhD, and Leong L. Ng MD^*

From the University of Leicester, Department of Cardiovascular Sciences (S.Q.K., O.S.D., R.J.O., P.A.Q., I.B.S., J.E.D., L.L.N.), Leicester Royal Infirmary, Leicester, UK; and Research Department (J.S., N.G.M., A.B.), BRAHMS Aktiengesellschaft, Hennigsdorf, Germany.

^* To whom correspondence should be addressed. E-mail: lln1{at}le.ac.uk.

Background--The role of the vasopressin system after acute myocardial infarction is unclear. Copeptin, the C-terminal part of the vasopressin prohormone, is secreted stoichiometrically with vasopressin. We compared the prognostic value of copeptin and an established marker, N-terminal pro-B-type natriuretic peptide (NTproBNP), after acute myocardial infarction.

Methods and Results--In this prospective single-hospital study, we recruited 980 consecutive post-acute myocardial infarction patients (718 men, median [range] age 66 [24 to 95] years), with follow-up over 342 (range 0 to 764) days. Plasma copeptin was highest on admission (n=132, P<0.001, day 1 versus days 2 to 5) and reached a plateau at days 3 to 5. In the 980 patients, copeptin (measured at days 3 to 5) was elevated in patients who died (n=101) or were readmitted with heart failure (n=49) compared with survivors (median [range] 18.5 [0.6 to 441.0] versus 6.5 [0.3 to 267.0] pmol/L, P<0.0005). With logistic regression analysis, copeptin (odds ratio, 4.14, P<0.0005) and NTproBNP (odds ratio, 2.26, P<0.003) were significant independent predictors of death or heart failure at 60 days. The area under the receiver operating characteristic curves for copeptin (0.75) and NTproBNP (0.76) were similar. The logistic model with both markers yielded a larger area under the curve (0.84) than for NTproBNP (P<0.013) or copeptin (P<0.003) alone, respectively. Cox modeling predicted death or heart failure with both biomarkers (log copeptin [hazard ratio, 2.33], log NTproBNP [hazard ratio, 2.70]). In patients stratified by NTproBNP (above the median of 900 pmol/L), copeptin above the median (7 pmol/L) was associated with poorer outcome (P<0.0005). Findings were similar for death and heart failure as individual end points.

Conclusions--The vasopressin system is activated after acute myocardial infarction. Copeptin may predict adverse outcome, especially in those with an elevated NTproBNP (more than 900 pmol/L).

Key words: heart failure • myocardial infarction • natriuretic peptides • peptides • plasma

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