Copeptin, miRNA-208, and miRNA-499 as New Biomarkers for Early Detection of Acute Coronary Syndrome.

Abstract

cTn and CK-MB are gold standard biomarkers for acute coronary syndrome (ACS) but are less sensitive in the first 3h 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 4h 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 3h and at 6h 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 3h (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 3h 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.