DISCUSSION
Unstable angina is a clinical condition that is responsible for around
16.6% of all ACS. On the ACS spectrum, its frequency falls below NSTEMI
and STEMI 13. Despite the fact that UA is an ACS type
with pronounced myocardial ischemia, there are no detectable circulating
cardiac biomarkers for its’ diagnosis (CK-MB, hsTn, Myoglobin)14 . The use of a new biomarker that can be used for
the early diagnosis and treatment of UA immediately after the onset of
ACS may be a valuable contribution to clinical practice. There are two
hypotheses for the increase in serum arginine vasopressin (AVP)/copeptin
levels in cases of ACS. The first is that it is an endocrine response to
acute stress, while the second suggests that inadequate filling of the
left ventricle caused by ACS stimulates cardiac baroreceptors or causes
direct damage to baroreceptors, subsequently leading to AVP and copeptin
secretion from the posterior pituitary gland 15,16 .
We found a statistically significant positive correlation between
patients’ serum copeptin levels and GRACE and SYNTAX scores the former
being as a prospectively studied scoring system for risk stratification
in patients with diagnosed UA/NSTEMI to estimate their in-hospital and
6-month to 3-year mortality and the latter which is the angiographic
indicator of CAD severity. There are many studies that have investigated
serum copeptin levels alone or in conjunction with hsTn levels in
relation to ACS diagnosis. Some studies demonstrated that patients who
had been admitted to the emergency services with chest pain, the use of
both serum troponin and copeptin levels increase the sensitivity and
negative predictive values in acute myocardial infarction diagnosis10,17,18 . Although Reichlin et al [10]
demonstrated that acute MI patients had significantly higher levels of
copeptin compared to UA patients, our study revealed the correlation
between copeptin levels and CAD severity in UA patients with negative
hsTn values. This finding may be important for the possible prognostic
value of copeptin in UA patients. Keller et al 17impressed the negative predictive value of copeptin levels for acute MI,
but they found that even in diabetic UA patients, copeptin levels were
high. This finding is compatible with ours, thus copeptin levels may
have diagnostic and even prognostic value in all spectrum of ACSs. Also,
Keller et al 17 demonstrated earlier increase in
copeptin levels than that of hsTn, which makes copeptin an important
biomarker for early diagnosis of acute MI. The diagnostic and prognostic
performances of copeptin were found to be additive to hsTn in NSTEMI,
independent of the effect of gender 18-20 .
In a large-scale study conducted by O’Malley et al 21,
which consisted of 4,432 patients, the use of multiple biomarkers,
including copeptin, was shown to be a strong prognostic factor of
outcomes such as cardiovascular death or heart failure in patients with
non-STE acute coronary syndromes.
In patients with STEMI, Reinstadler et al 22 found an
association between higher serum copeptin levels and acute and chronic
infarct size, reduced left ventricular ejection fraction, and adverse
remodeling during follow-ups. Although our study used a different
patient population, its findings support those of Reinstadler et al. Our
study found increased copeptin levels were associated with more severe
CAD, this may also explain why increased copeptin levels resulted in
worse left ventricular systolic performance and adverse remodeling.
In our study, we did not use a control group with individuals undergoing
elective coronary angiography due to stable coronary artery disease.
This was firstly because we were seeking to determine any correlation
between different copeptin levels and clinical and angiographic disease
levels among patients with similar clinical symptoms who had been
diagnosed with UA after being admitted to an emergency room. Secondly,
it has already been reported that stable coronary artery disease
patients have shown increased copeptin levels 23 .
When evaluating the study data in detail, the mean serum copeptin levels
in patients with non-critical CAD or normal coronary arteries were found
to be 9.4 pmol/l. In our study, the low mean values for copeptin levels
and SYNTAX scores in group 1 are consistent with the existing
literature. Zellweger et al 24 found 9 pmol/l as a
prognostic cut-off value, above which 2-year mortality was significantly
higher in diabetic acute MI patients. They concluded that copeptin
levels predicted mortality more accurately when used in conjunction with
hsTn. In many studies, when the threshold serum copeptin level was
<14 pmol/l, the negative predictive value for ACS has been
found to reach 97%, while the p value has been shown to be
statistically significant 10,25,26 .
In our study, the threshold value of 18.3 pmol/l, which was selected to
predict a high SYNTAX score, is consistent with the literature. In a
study that sought to detect non-ST segment elevation acute coronary
syndrome patients in emergency room situations, Morawiec et al27 found that 17.4 pmol/l to be the threshold copeptin
value. Reinstadler et al 22, who studied STEMI
patients, found that the threshold copeptin level which was a predictor
of poor left ventricular ejection fraction and adverse remodeling was
16.7 pmol/l.