cTn and CK-MB are gold standard
biomarkers for
acute coronary syndrome (ACS) but are less sensitive in the first 3 h after onset of symptoms. A need thus exists for novel
biomarkers for early detection of ACS. We evaluated circulating copeptin, miRNA-208, and miRNA-499 as possible
biomarkers for early detection of
unstable angina (UA) and non-
ST-segment elevation myocardial infarction (
NSTEMI). Sixty-five patients with probable ACS that presented within 4 h of the onset of
chest pain (23 UA and 42
NSTEMI) and 25 apparently healthy individuals were studied. Two sets of blood samples collected in the first 3 h and at 6 h after onset were analyzed for copeptin levels via ELISA and miRNA-208 and miRNA-499 expression via real-time PCR. Copeptin, miRNA-208, and miRNA-499 expression levels were significantly increased in UA and
NSTEMI patients compared with controls (p < 0.001) and in NSTEMT compared with UA patients (p < 0.001). Levels were also significantly elevated in UA and
NSTEMI patients with negative cardiac
troponin in the first 3 h (p < 0.001). ROC curves displayed AUC for prediction of ACS of 0.96 for copeptin, 0.97 for miRNA-208, and 0.97 for miRNA-499. Their combination improved AUC to 0.98. Copeptin and miRNA-208 and miRNA-499 expression are promising
biomarkers for UA and
NSTEMI that present in the first 3 h of
pain onset. A combination of these markers with
cTn may increase the accuracy of diagnosis by avoiding the gray zone of
cTn as a
biomarker.