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.