{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:10:47Z","timestamp":1760235047323,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The \u201cCan Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC\/AHA guidelines\u201d (CRUSADE) score emerged as a predictor of major bleeding in patients presenting with the acute coronary syndrome. On the other hand, previous studies established the association of dephosphorylated-uncarboxylated Matrix Gla protein (dp-ucMGP) and vitamin K, as well as their subsequent impact on coagulation cascade and bleeding tendency. Therefore, in the present study, we explored if dp-ucMGP plasma levels were associated with CRUSADE bleeding score. In this cross-sectional study, physical examination and clinical data, including plasma dp-ucMGP levels, were obtained from 80 consecutive patients with acute myocardial infarction (AMI). A significant positive correlation was found between CRUSADE bleeding score and both dp-ucMGP plasma levels (r = 0.442, p &lt; 0.001) and risk score of in-hospital mortality (r = 0.520, p &lt; 0.001), respectively. In comparing the three risk groups of risk for in-hospital bleeding, the high\/very high-risk group had significantly higher dp-ucMGP levels from both very low\/low group (1277 vs. 794 pmol\/L, p &lt; 0.001) and the moderate group (1277 vs. 941 pmol\/L, p = 0.047). Overall, since higher dp-ucMGP levels were associated with elevated CRUSADE score and prolonged hemostasis parameters, this may suggest that there is a biological link between dp-ucMGP plasma levels and the risk of bleeding in patients who present with AMI.<\/jats:p>","DOI":"10.3390\/life11080733","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T10:31:44Z","timestamp":1627036304000},"page":"733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Dephosphorylated-Uncarboxylated Matrix Gla Protein and Risk of Major Bleeding in Patients Presenting with Acute Myocardial Infarction"],"prefix":"10.3390","volume":"11","author":[{"given":"Admira","family":"Bilalic","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina Ticinovic","family":"Kurir","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4878-8146","authenticated-orcid":false,"given":"Josip A.","family":"Borovac","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Split, 21000 Split, Croatia"},{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9696-3359","authenticated-orcid":false,"given":"Marko","family":"Kumric","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-3182","authenticated-orcid":false,"given":"Daniela","family":"Supe-Domic","sequence":"additional","affiliation":[{"name":"Department of Health Studies, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5433-5063","authenticated-orcid":false,"given":"Marino","family":"Vilovic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinko","family":"Martinovic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-0635","authenticated-orcid":false,"given":"Josko","family":"Bozic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kumri\u0107, M., Ti\u010dinovi\u0107 Kurir, T., Borovac, J.A., and Bo\u017ei\u0107, J. (2020). The Role of Natural Killer (NK) Cells in Acute Coronary Syndrome: A Comprehensive Review. Biomolecules, 10.","DOI":"10.3390\/biom10111514"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"256","DOI":"10.21037\/atm.2016.06.33","article-title":"Epidemiology of coronary heart disease and acute coronary syndrome","volume":"4","author":"Leischik","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hamm, C.W., M\u00f6llmann, H., Bassand, J.P., and Van de Werf, F. (2009). Acute coronary syndrome. The ESC Textbook of Cardiovascular Medicine, Oxford University Press. [2nd ed.].","DOI":"10.1093\/med\/9780199566990.003.016"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1016\/j.jacc.2014.09.017","article-title":"2014 AHA\/ACC Guideline for the management of patients with non-ST-elevation acute coronary syndromes. A report of the American College of Cardiology\/American Heart Association Task Force on practice guidelines","volume":"64","author":"Amsterdam","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1093\/eurheartj\/ehm019","article-title":"Bleeding and blood transfusion issues in patients with non-ST-segment elevation acute coronary syndromes","volume":"28","author":"Rao","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1161\/CIRCULATIONAHA.108.828541","article-title":"Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: The CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC\/AHA Guidelines) bleeding score","volume":"119","author":"Subherwal","year":"2009","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/2048872612469885","article-title":"Comparison of the performance of the CRUSADE, ACUITY-HORIZONS, and ACTION bleeding risk scores in STEMI undergoing primary PCI: Insights from a cohort of 1391 patients","volume":"2","year":"2013","journal-title":"Eur. Heart J. Acute Cardiovasc. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"B161","DOI":"10.1016\/j.jacc.2012.08.591","article-title":"TCT-557 the risk of in-hospital bleeding and long-term mortality in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention","volume":"60","author":"Boden","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1253\/circj.CJ-12-1177","article-title":"Simple risk algorithm to predict serious bleeding in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: RISK-PCI bleeding score","volume":"77","author":"Mrdovic","year":"2013","journal-title":"Circ. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.ihj.2016.03.007","article-title":"CRUSADE bleeding score as a predictor of bleeding events in patients with acute coronary syndrome in Zagazig University Hospital","volume":"68","author":"Farag","year":"2016","journal-title":"Indian Heart J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.hlc.2014.05.002","article-title":"Use of the CRUSADE bleeding risk score in the prediction of major bleeding for patients with acute coronary syndrome receiving enoxaparin in Thailand","volume":"23","author":"Jinatongthai","year":"2014","journal-title":"Heart Lung Circ."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3109\/17482941.2011.567287","article-title":"Comparison of ischemic and bleeding risk scores in non-ST elevation acute coronary syndromes","volume":"13","author":"Amador","year":"2011","journal-title":"Acute Card. Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1161\/CIRCRESAHA.108.183053","article-title":"Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries","volume":"104","author":"Speer","year":"2009","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.3748\/wjg.v26.i32.4866","article-title":"Inactive matrix Gla protein is elevated in patients with inflammatory bowel disease","volume":"26","author":"Brnic","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1111\/j.1538-7836.2007.02758.x","article-title":"Post-translational modifications regulate matrix Gla protein function: Importance for inhibition of vascular smooth muscle cell calcification","volume":"5","author":"Schurgers","year":"2007","journal-title":"Thromb. Haemost."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.atherosclerosis.2012.09.019","article-title":"The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein","volume":"225","author":"Dalmeijer","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1002\/pro.5560030511","article-title":"Conserved phosphorylation of serines in the Ser-X-Glu\/Ser(P) sequences of the vitamin K-dependent matrix Gla protein from shark, lamb, rat, cow, and human","volume":"3","author":"Price","year":"1994","journal-title":"Protein Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/0006-291X(83)91663-7","article-title":"Matrix Gla protein, a new gamma-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone","volume":"117","author":"Price","year":"1983","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14971","DOI":"10.1016\/S0021-9258(18)95688-7","article-title":"Primary structure of bovine matrix Gla protein, a new vitamin K-dependent bone protein","volume":"260","author":"Price","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1160\/TH09-11-0786","article-title":"Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species","volume":"104","author":"Cranenburg","year":"2010","journal-title":"Thromb. Haemost."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/eurheartj\/ehx393","article-title":"ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)","volume":"39","author":"Ibanez","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_22","first-page":"ehaa575","article-title":"ESC Scientific Document Group. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation","volume":"37","author":"Collet","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1161\/01.CIR.91.6.1659","article-title":"Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction. Results from an international trial of 41,021 patients. GUSTO-I Investigators","volume":"91","author":"Lee","year":"1995","journal-title":"Circulation"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Schurgers, L.J., Joosen, I.A., Laufer, E.M., Chatrou, M.L., Herfs, M., Winkens, M.H., Westenfeld, R., Veulemans, V., Krueger, T., and Shanahan, C.M. (2012). Vitamin K-antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043229"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.jnutbio.2012.02.012","article-title":"Circulating matrix Gla protein is associated with coronary artery calcification and vitamin K status in healthy women","volume":"24","author":"Dalmeijer","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.atherosclerosis.2014.04.027","article-title":"Desphospho-uncarboxylated matrix Gla-protein is associated with mortality risk in patients with chronic stable vascular disease","volume":"235","author":"Mayer","year":"2014","journal-title":"Atherosclerosis"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1161\/HYPERTENSIONAHA.119.12412","article-title":"Vitamin K-Dependent Matrix Gla Protein as Multifaceted Protector of Vascular and Tissue Integrity","volume":"73","author":"Wei","year":"2019","journal-title":"Hypertension"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1111\/jth.13306","article-title":"Increased risk of major bleeding after a minor bleed during treatment with vitamin K antagonists is determined by fixed common risk factors","volume":"14","author":"Reitsma","year":"2016","journal-title":"J. Thromb. Haemost."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"864","DOI":"10.4065\/82.7.864","article-title":"How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults","volume":"82","author":"Kamal","year":"2007","journal-title":"Mayo Clin. Proc."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Bilalic, A., Ticinovic Kurir, T., Kumric, M., Borovac, J.A., Matetic, A., Supe-Domic, D., and Bozic, J. (2021). Circulating Levels of Dephosphorylated-Uncarboxylated Matrix Gla Protein in Patients with Acute Coronary Syndrome. Molecules, 26.","DOI":"10.3390\/molecules26041108"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jjcc.2010.01.010","article-title":"Differences in intravascular ultrasound findings in culprit lesions in infarct-related arteries between ST segment elevation myocardial infarction and non-ST segment elevation myocardial infarction","volume":"56","author":"Hong","year":"2010","journal-title":"J. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.2174\/0929867325666180716104159","article-title":"The Role of Matrix Gla Protein (MGP) in Vascular Calcification","volume":"27","author":"Svanberg","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1042\/CS20100589","article-title":"Circulating levels of non-phosphorylated undercarboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure","volume":"121","author":"Ueland","year":"2011","journal-title":"Clin. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ijcard.2019.05.035","article-title":"Combinations of bleeding and ischemic risk and their association with clinical outcomes in acute coronary syndrome","volume":"290","author":"Mohamed","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijcard.2017.07.095","article-title":"Additive value of the CRUSADE score to the GRACE score for mortality risk prediction in patients with acute coronary syndromes","volume":"245","author":"Cordero","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/j.hlc.2020.04.008","article-title":"Meta-Analysis of Bleeding Scores Performance for Acute Coronary Syndrome","volume":"29","author":"Wang","year":"2020","journal-title":"Heart Lung Circ."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/8\/733\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:34:03Z","timestamp":1760164443000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/11\/8\/733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,23]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["life11080733"],"URL":"https:\/\/doi.org\/10.3390\/life11080733","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2021,7,23]]}}}