{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T08:20:46Z","timestamp":1783066846366,"version":"3.54.6"},"reference-count":33,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Early identification of anatomically significant coronary artery disease (CAD) remains a major clinical challenge despite advances in cardiovascular diagnostics. Novel circulating biomarkers may improve risk stratification and diagnostic discrimination beyond conventional parameters. We investigated the diagnostic utility of four emerging biomarkers\u2014Phoenixin-14, Syntenin-1, Alamandine, and Cerebellin-1\u2014for the assessment of CAD severity. In this prospective observational study, 90 participants undergoing coronary angiography were categorized into three groups: severe CAD (\u226570% stenosis; n = 30), non-obstructive\/non-critical CAD (&lt;70% stenosis; n = 30), and angiographically normal controls (n = 30). Patients with acute coronary syndrome, diabetes mellitus, prior coronary revascularization, cardiomyopathy, or significant systemic disease were excluded. Circulating biomarker concentrations were quantified using the enzyme-linked immunosorbent assay. Comparative analyses, correlation testing, and receiver operating characteristic (ROC) analyses were performed to evaluate discriminatory performance. Circulating Phoenixin-14 concentrations progressively declined across the control, non-critical CAD, and severe CAD groups [40.1 (29.0\u201349.7) vs. 24.4 (18.5\u201330.1) vs. 16.7 (13.4\u201319.0) pg\/mL, respectively; p &lt; 0.001]. Phoenixin-14 demonstrated outstanding discrimination for severe CAD, achieving an area under the ROC curve (AUC) of 0.969 (95% CI, 0.888\u20130.997), with 86.7% sensitivity and 96.7% specificity at a threshold of \u226420.2 pg\/mL. Diagnostic performance was substantially lower for Syntenin-1 (AUC, 0.795), Alamandine (AUC, 0.661), and Cerebellin-1 (AUC, 0.597). Phoenixin-14 also showed robust discrimination for non-critical CAD (AUC, 0.832). Biomarker concentrations exhibited correlations with metabolic indices while remaining largely independent of traditional cardiovascular risk factors. Among the evaluated novel circulating biomarkers, Phoenixin-14 demonstrated superior diagnostic performance for both obstructive and non-obstructive CAD, markedly outperforming Syntenin-1, Alamandine, and Cerebellin-1. These findings identify Phoenixin-14 as a promising candidate biomarker for CAD severity assessment and clinical risk stratification. Larger multicenter studies are warranted to validate these exploratory findings and determine their incremental value in contemporary cardiovascular practice.<\/jats:p>","DOI":"10.3390\/ijms27135719","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:48:16Z","timestamp":1782366496000},"page":"5719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced Discrimination of Coronary Artery Disease Severity by Circulating Phoenixin-14: Evidence from a Clinical Laboratory Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5879-3494","authenticated-orcid":false,"given":"\u0130smail","family":"Polat","sequence":"first","affiliation":[{"name":"Department of Cardiology, Fethi Sekin City Hospital, 23119 Elazig, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3997-2969","authenticated-orcid":false,"given":"Bekir","family":"Dagdeviren","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Firat University, 23119 Elazig, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1713-3451","authenticated-orcid":false,"given":"Mehdi","family":"Karasu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fethi Sekin City Hospital, 23119 Elazig, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2508-6707","authenticated-orcid":false,"given":"\u00d6mer","family":"Bedir","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Adana City Training and Research Hospital, 01000 Adana, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suna","family":"Aydin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Fethi Sekin City Hospital, 23119 Elazig, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5659-3499","authenticated-orcid":false,"given":"Elif","family":"Emre","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, F\u0131rat University, 23119 Elazig, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6431-643X","authenticated-orcid":false,"given":"Musa","family":"Sari","sequence":"additional","affiliation":[{"name":"Department of Biology (Molecular Biology), Faculty of Science, Sivas Cumhuriyet University, 58000 Sivas, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zlem","family":"Se\u00e7en","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fethi Sekin City Hospital, 23119 Elazig, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9956-1029","authenticated-orcid":false,"given":"\u00c7etin","family":"Mirzaoglu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fethi Sekin City Hospital, 23119 Elazig, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6162-3250","authenticated-orcid":false,"given":"Suleyman","family":"Aydin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, F\u0131rat University, 23119 Elazig, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990\u20132019: Update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J. 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