25
| 1 | 2012
Klinisk Biokemi i Norden
(
Fortsætter side 26)
The first study on copeptin measurement in AMI
patients suggested that plasma copeptin concentrations
peak during the first day after admission and decreases
during the following days. In addition, copeptin concen-
trations were correlated to later death or development
of heart failure (10), a conclusion that has been confir-
med in later studies (11). This finding was followed by
a study that examined copeptin measurement in the
early diagnosis of AMI using blood samples from 487
consecutive patients admitted to the emergency room
(
ER) with acute chest pain (12). This study showed that
copeptin concentrations in plasma peak 0-4 hours after
onset of symptoms, which is within the time span where
troponin concentrations are often inconclusive. In agre-
ement with previous observations, copeptin declined in
AMI patients during the first 12 hours while troponin
T concentrations increased. The fact that copeptin
concentrations were increased at times when troponin
T remained low resulted in a negative predictive power
of 99% at presentation if troponin T and copeptin mea-
surement were used in combination. This finding has
been confirmed in the APACE study of 1386 patients
with suspected acute coronary syndrome. Copeptin
measurement improved the diagnostic performance
defined as AUC from receiver-operating curves from
0.77
for troponin Tmeasurement alone to 0.91 with the
combination of copeptin and troponin Tmeasurements
(13).
Notably, these two studies employed conventional
troponin assays that are unable to measure down to the
99
th
percentile. High-sensitive troponin assays are able
to exclude AMI earlier and with higher negative pre-
dictive values compared to conventional troponin assays
(7)
that could potentially preclude a need for copeptin
analysis. In agreement with this possibility, the added
benefit of copeptin was attenuated when the APACE
study were reanalyzed using a high-sensitive troponin I
assay. Another problem was that these studies included
AMI patients with diagnostic ECG changes (STEMI)
that usually are not subject to biomarker analysis.
Patients with STEMI have larger infarct volumes (14)
and this could potentially overestimate the diagnostic
performance of copeptin. Recently, one study showed
that copeptin concentrations below 14 pmol/L, early
after admission, add information to high-sensitive tro-
ponin T measurements with negative predictive values
approaching 99% also when STEMI patients were
excluded (15). This finding has also been confirmed
in a smaller study (16). The prevalence of AMI was
between 9% and 27% in these positive studies. In the
ROMICAT study, however, where the AMI prevalence
was 2%, copeptin measurement did not add diagnostic
power when combined with high-sensitive troponin
T (17). It is possible though, that the low prevalence
of AMI in this study and the fact that the first blood
sample was often taken over 4 hours after admission
impaired the diagnostic power of copeptin. The high
negative predictive value in the four positive studies
comes with a cost of impaired diagnostic accuracy with
positive predictive values often below 50%. This is likely
due to copeptin elevations being relatively common
among chest pain patients, also in the absence of AMI.
However, if the combination of negative copeptin and
negative troponin concentrations can safely exclude
AMI in 25-30% of the chest pain patients at admission
as indicated in some studies (13,15), copeptin will add
clinical value. In contrast to troponin, copeptin concen-
trations do not increase with age (18), which introduces
the possibility that copeptin measurement may be espe-
cially helpful to exclude AMI in older patient groups.
The most important question for future clinical trials
is now to verify that it is safe to exclude AMI based on
low copeptin concentrations in plasma.
Copeptin in heart failure
Heart failure is a common condition that affects almost
2%
of the Western population. Although medical tre-
atment of heart failure has changed dramatically over
the last decades, there is still no significant improve-
ment in long-term survival, and the 5 year mortality
is still ~50%. With this in mind, there is a need for
tools that can identify patients at high risk of clini-
cal deterioration and death. Copeptin measurement
in heart failure may be such a tool, where otherwise
natriuretic peptide measurement has been suggested
for risk estimation. In a Scandinavian study on elderly
patients presenting with symptoms of heart failure,
increased copeptin concentrations alone or combined
with increased natriuretic peptides (NT-proBNP) were
strongly associated with increase of all-cause mortality
in a follow up period of 13 years (19). Notably, this
study included 470 elderly people (average patient
age of 73 years) in the primary setting, which is where
most heart failure patients are diagnosed, treated, and
followed. Other studies have shown similar prognostic
power of copeptin measurement in more selected heart
failure patient groups (20-22).
A particular use of copeptin measurement in heart
