{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:30:27Z","timestamp":1790443827404,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 HL124266"],"award-info":[{"award-number":["R01 HL124266"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Circulating monocytes have different subsets, including classical (CD14++CD16\u2212), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++), which play different roles in cardiovascular physiology and disease progression. The predictive value of each subset for adverse clinical outcomes in patients with coronary artery disease is not fully understood. We sought to evaluate the prognostic efficacy of each monocyte subset in patients with ST-elevation myocardial infarction (STEMI). We recruited 100 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). Blood samples were collected at the time of presentation to the hospital (within 6 h from onset of symptoms, baseline (BL)) and then at 3, 6, 12, and 24 h after presentation. Monocytes were defined as CD45+\/HLA-DR+ and then subdivided based on the expression of CD14, CD16, CCR2, CD11b, and CD42. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, stent thrombosis, in-stent restenosis, and recurrent myocardial infarction. Univariate and multivariate Cox proportional hazards models, including baseline comorbidities, were performed. The mean age of our cohort was 58.9 years and 25% of our patients were females. Patients with high levels (above the median) of CD14+CD16++ monocytes showed an increased risk for the primary endpoint in comparison to patients with low levels; adjusted hazard ratio (aHR) for CD14+\/CD16++ cells was 4.3 (95% confidence interval (95% CI) 1.2\u201314.8, p = 0.02), for CD14+\/CD16++\/CCR2+ cells was 3.82 (95% CI 1.06\u201313.7, p = 0.04), for CD14+\/CD16++\/CD42b+ cells was 3.37 (95% CI 1.07\u201310.6, p = 0.03), for CD14+\/CD16++\/CD11b+ was 5.17 (95% CI 1.4\u201318.0, p = 0.009), and for CD14+ HLA-DR+ was 7.5 (95% CI 2.0\u201328.5, p = 0.002). CD14++CD16\u2212, CD14++CD16+, and their CD11b+, CCR2+, and CD42b+ aggregates were not significantly predictive for our composite endpoint. Our study shows that CD14+ CD16++ monocytes and their subsets expressing CCR2, CD42, and CD11b could be important predictors of clinical outcomes in patients with STEMI. Further studies with a larger sample size and different coronary artery disease phenotypes are needed to verify the findings.<\/jats:p>","DOI":"10.3390\/ijms241411342","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T01:43:22Z","timestamp":1689212602000},"page":"11342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Prognostic Significance of Activated Monocytes in Patients with ST-Elevation Myocardial Infarction"],"prefix":"10.3390","volume":"24","author":[{"given":"Mohamed","family":"Abo-Aly","sequence":"first","affiliation":[{"name":"Gill Heart and Vascular Institute, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Cardiovascular Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elica","family":"Shokri","sequence":"additional","affiliation":[{"name":"Gill Heart and Vascular Institute, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshman","family":"Chelvarajan","sequence":"additional","affiliation":[{"name":"Gill Heart and Vascular Institute, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadea M.","family":"Tarhuni","sequence":"additional","affiliation":[{"name":"Canadian Cardiac Research Center, Department of Internal Medicine, Division of Cardiology, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himi","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Gill Heart and Vascular Institute, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Cardiovascular Division, Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8178-7102","authenticated-orcid":false,"given":"Ahmed","family":"Abdel-Latif","sequence":"additional","affiliation":[{"name":"Gill Heart and Vascular Institute, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Cardiovascular Division, Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,12]]},"reference":[{"key":"ref_1","first-page":"e85","article-title":"Heart disease and stroke statistics\u20132006 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee","volume":"113","author":"Thom","year":"2006","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1136\/hrt.2010.200261","article-title":"The NCDR ACTION Registry-GWTG: Transforming contemporary acute myocardial infarction clinical care","volume":"96","author":"Peterson","year":"2010","journal-title":"Heart"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e012188","DOI":"10.1161\/JAHA.119.012188","article-title":"Prognostic Implications of Door-to-Balloon Time and Onset-to-Door Time on Mortality in Patients with ST -Segment-Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention","volume":"8","author":"Park","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1056\/NEJM199902113400607","article-title":"Acute-phase proteins and other systemic responses to inflammation","volume":"340","author":"Gabay","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1056\/NEJMoa012295","article-title":"Widespread coronary inflammation in unstable angina","volume":"347","author":"Buffon","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"C761","DOI":"10.1152\/ajpcell.00326.2020","article-title":"Nonclassical monocytes in cardiovascular physiology and disease","volume":"320","author":"Tahir","year":"2021","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1161\/CIRCGENETICS.111.960385","article-title":"Elevated CD14++CD16\u2212 monocytes predict cardiovascular events","volume":"5","author":"Berg","year":"2012","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/jcbfm.2009.25","article-title":"Monocyte subtypes predict clinical course and prognosis in human stroke","volume":"29","author":"Urra","year":"2009","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1126\/science.1142883","article-title":"Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior","volume":"317","author":"Auffray","year":"2007","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1161\/ATVBAHA.118.311022","article-title":"Human Monocyte Heterogeneity as Revealed by High-Dimensional Mass Cytometry","volume":"39","author":"Hamers","year":"2019","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/art.33418","article-title":"The CD14(bright) CD16+ monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population","volume":"64","author":"Rossol","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.jacc.2012.07.019","article-title":"CD14++CD16+ monocytes independently predict cardiovascular events: A cohort study of 951 patients referred for elective coronary angiography","volume":"60","author":"Rogacev","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1365-2567.2009.03224.x","article-title":"Differential regulation of toll-like receptor-2, toll-like receptor-4, CD16 and human leucocyte antigen-DR on peripheral blood monocytes during mild and severe dengue fever","volume":"130","author":"Azeredo","year":"2010","journal-title":"Immunology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1161\/ATVBAHA.120.314807","article-title":"NETosis Is Required for S100A8\/A9-Induced Granulopoiesis after Myocardial Infarction","volume":"40","author":"Nagareddy","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1161\/CIRCULATIONAHA.119.043833","article-title":"Neutrophil-Derived S100A8\/A9 Amplify Granulopoiesis after Myocardial Infarction","volume":"141","author":"Sreejit","year":"2020","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1136\/heartjnl-2021-319225","article-title":"Prognostic value of admission high-sensitivity troponin in patients with ST-elevation myocardial infarction","volume":"107","author":"Georgiopoulos","year":"2021","journal-title":"Heart"},{"key":"ref_18","first-page":"1082","article-title":"2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation","volume":"70","author":"Ibanez","year":"2017","journal-title":"Rev. Esp. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1136\/heartjnl-2021-320030","article-title":"Do we need early risk stratification after ST-elevation myocardial infarction?","volume":"107","author":"McLeod","year":"2021","journal-title":"Heart"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.yjmcc.2020.09.011","article-title":"Autotaxin inhibition reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction","volume":"149","author":"Tripathi","year":"2020","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0735-1097(01)01721-1","article-title":"Prognostic significance of peripheral monocytosis after reperfused acute myocardial infarction: A possible role for left ventricular remodeling","volume":"39","author":"Maekawa","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1016\/j.jacc.2009.08.089","article-title":"Impaired infarct healing in atherosclerotic mice with Ly-6C(hi) monocytosis","volume":"55","author":"Panizzi","year":"2010","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1038\/nm.3284","article-title":"B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction","volume":"19","author":"Zouggari","year":"2013","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nature11260","article-title":"Myocardial infarction accelerates atherosclerosis","volume":"487","author":"Dutta","year":"2012","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"741890","DOI":"10.3389\/fcvm.2021.741890","article-title":"Circulating Monocyte Subsets Are Associated with Extent of Myocardial Injury but not with Type of Myocardial Infarction","volume":"8","author":"Askari","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1161\/ATVBAHA.114.304652","article-title":"Monocytes in myocardial infarction","volume":"35","author":"Dutta","year":"2015","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16304","DOI":"10.1038\/s41598-019-52671-y","article-title":"Neutrophil extracellular traps and monocyte subsets at the culprit lesion site of myocardial infarction patients","volume":"9","author":"Mangold","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1111\/j.1538-7836.2011.04603.x","article-title":"The CD14++CD16+ monocyte subset and monocyte-platelet interactions in patients with ST-elevation myocardial infarction","volume":"10","author":"Tapp","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e3466","DOI":"10.1097\/MD.0000000000003466","article-title":"The Kinetics of Circulating Monocyte Subsets and Monocyte-Platelet Aggregates in the Acute Phase of ST-Elevation Myocardial Infarction: Associations with 2-Year Cardiovascular Events","volume":"95","author":"Zhou","year":"2016","journal-title":"Medicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1002\/JLB.5A0420-231RR","article-title":"Monocyte subsets predict mortality after cardiac arrest","volume":"109","author":"Krychtiuk","year":"2021","journal-title":"J. Leukoc. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1161\/01.CIR.0000015700.27754.6F","article-title":"Increased platelet binding to circulating monocytes in acute coronary syndromes","volume":"105","author":"Sarma","year":"2002","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1160\/TH09-01-0023","article-title":"The role of monocytes in thrombotic disorders. Insights from tissue factor, monocyte-platelet aggregates and novel mechanisms","volume":"102","author":"Shantsila","year":"2009","journal-title":"Thromb. Haemost."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. Jama, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11342\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:11:08Z","timestamp":1760127068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/14\/11342"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,12]]},"references-count":33,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["ijms241411342"],"URL":"https:\/\/doi.org\/10.3390\/ijms241411342","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,12]]}}}