A Novel Biomarker for Heart Failure, Acute Myocardial Infraction and LRTI.
A fragment of Prepro-AVP(126-164) (Human)
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
approximately 900 pmol/L), copeptin above the median ( approximately 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 approximately 900 pmol/L).
Khan et al. Circulation. 2007 Apr 24;115(16):2103-10.
BACKGROUND: The aim of the present
study was to evaluate the capability B-type natriuretic peptide (BNP)
as a prognostic marker in patients with acute destabilized heart failure
in comparison with mid-regional pro-A-type natriuretic peptide (MR-proANP),
mid-regional pro-adrenomedullin (MR-proADM), and the C-terminal part
of the arginine vasopressin prohormone (Copeptin).
METHODS AND RESULTS: BNP, MR-proANP, MR-proADM, and Copeptin plasma concentrations were obtained
in 137 patients with acute destabilized heart failure attending a tertiary
care hospital. The end point was defined as all-cause mortality, and
the study participants were followed for 365 days. Of the 137 patients
enrolled, 41 died and 96 survived during follow-up. ROC curve analysis
showed that the areas under curve for the prediction of 1-year mortality
were similar for BNP (0.716; 95% CI 0.633-0.790), MR-proANP (0.725; 95%
CI 0.642-0.798), MR-proADM (0.708; 95% CI 0.624-0.782), and Copeptin
(0.688; 95% CI 0.603-0.764). Using tercile approaches, Kaplan-Meier curve
analyses demonstrated that the predictive value of all four analytes
for survival probability was comparable (log-rank test for trend, P < .001
for each). In multivariable Cox proportional-hazards regression analyses,
increased BNP, MR-proANP, MR-proADM, and Copeptin plasma concentrations
were the strongest predictors of mortality.
CONCLUSION: BNP is considered
an established prognostic marker for heart failure patients. The present
study provides evidence that MR-proANP, MR-proADM, and Copeptin measurements
might have similar predictive properties compared with BNP determinations
for one-year all-cause mortality in acute destabilized heart failure.
Gegenhuber et al. J Card Fail. 2007 Feb;13(1):42-9.
BACKGROUND: Vasopressin has haemodynamic
as well as osmoregulatory effects, and reflects the individual stress
response. Copeptin is co-synthesized with vasopressin, directly mirroring
vasopressin levels, but is more stable in plasma and serum. Both levels
are increased in patients with septic shock. Lower respiratory tract
infections (LRTI) are a precursor of sepsis. Thus, we investigated circulating
levels and the prognostic use of copeptin for the severity and outcome
in patients with LRTI.
MATERIALS AND METHODS: Five hundred and forty-five
consecutive patients with LRTI and 50 healthy controls were evaluated.
Serum copeptin levels were measured with a new chemiluminescent sandwich
immunoassay. RESULTS: Of the 545 patients, 373 had community-acquired
pneumonia (CAP), 60 acute exacerbations of chronic obstructive pulmonary
disease (COPD), 59 acute bronchitis, 13 exacerbations of asthma and 40
other final diagnoses. Copeptin levels were significantly higher in patients
with LRTI as compared to controls (P < 0.001) with
highest levels in patients with CAP. Copeptin levels increased with increasing
severity of CAP, as classified by the pneumonia severity index (PSI) (P < 0.001).
In patients who died, copeptin levels on admission were significantly higher
as compared to levels in survivors [70.0 (28.8-149.0) vs. 24.3 (10.8-43.8)
pmol L(-1), P
< 0.001]. The area under the receiver operating curve (AUC) for
survival was 0.75 for copeptin, which was significantly higher as compared
to C-reactive protein (AUC 0.61, P = 0.01), leukocyte count (AUC 0.59,
P = 0.01) and similar to procalcitonin (AUC 0.68, P = 0.21).
CONCLUSIONS: Copeptin levels are increased with increasing severity of LRTI namely
in patients with CAP and unfavourable outcome. Copeptin levels, as
a novel biomarker, might be a useful tool in the risk stratification
of patients with LRTI.
Müller et al. Eur J Clin Invest. 2007 Feb;37(2):145-52.
BACKGROUND: Natriuretic peptides,
particularly brain natriuretic peptide BNP, are elevated in heart failure
and therefore considered to be excellent predictors of outcome. Vasopressin
is also known to be related to the severity of heart disease. Copeptin--an
inactive fragment of the vasopressin precursor--has not been previously
investigated in the context of heart failure.
MATERIALS AND METHODS: We prospectively studied 268 patients with advanced heart failure after
they had been discharged from the hospital. We investigated the ability
of BNP and copeptin to predict death, re-hospitalization due to heart
failure, and a combination of the two endpoints. RESULTS: Over a mean
follow-up period of 15.8 months (up to 24 months), 83 patients died,
122 patients experienced worsening of heart failure, and 145 patients
achieved the combined endpoint. Univariate predictors of death were copeptin,
BNP, age and impaired kidney function. In multivariate analysis, copeptin
(chi(2) = 16, P < 0.0001) and age (chi(2) = 4, P < 0.05) were independent predictors. Univariate predictors of re-hospitalization due to heart failure were copeptin, BNP, age and impaired kidney function. Furthermore, in multivariate analysis BNP (chi(2) = 18, P < 0.0001), age (chi(2) = 11.8, P < 0.001) and copeptin (chi(2) = 4.2, P < 0.05)
were found to be independent predictors.
CONCLUSION: Our study is the
first to show that copeptin is an excellent predictor of outcome in advanced
heart failure patients. Its value is superior to that of BNP in predicting
death and a combined endpoint, although BNP is still suitable for predicting
chronic heart failure (CHF) re-hospitalization. Our data imply that
vasopressin antagonism might be a new target to improve outcome in this
Stoiser et al. Eur J Clin Invest. 2006 Nov;36(11):771-8.
BACKGROUND: Arginine vasopressin
(AVP) is a key regulator of water balance, but its instability makes
reliable measurement difficult and precludes routine use. We present
a method for quantifying AVP release by use of copeptin, a glycopeptide
comprising the C-terminal part of the AVP prohormone.
measured copeptin in 50 µL serum and plasma samples from healthy
individuals and from critically ill patients with sepsis. Our sandwich
immunoluminometric assay used 2 polyclonal antibodies to amino acids
132-164 of pre-provasopressin. RESULTS: The assay yielded results
within 3 h. The analytical detection limit was 1.7 pmol/L, and the
interlaboratory CV was <20% for values >2.25 pmol/L. The assay was linear
on dilution of the analyte. Ex vivo copeptin stability (<20%
loss of analyte) for at least 7 days at room temperature and
14 days at 4 degrees C was shown for serum and EDTA-, heparin-,
and citrate plasma. Copeptin (median, 4.2 pmol/L; range, 1-13.8
pmol/L) was detectable in 97.5% of 359 healthy individuals and
was not associated with age. Median concentrations were considerably
higher in men than women, increased significantly after exercise,
and were influenced by fasting and water load. Copeptin was significantly
(P <0.001) increased in 60 critically ill patients with sepsis
(median, 79.5 pmol/L; range, 10.6-228.0 pmol/L). The correlation
between copeptin and AVP for 110 samples was r = 0.78 (P <0.0001).
CONCLUSIONS: Copeptin is stable for days after blood withdrawal
and can be quickly and easily measured. The copeptin assay may
be a useful alternative to direct measurement of AVP concentration.
Morgenthaler et al. Clin Chem. 2006 Jan;52(1):112-9.