{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:11:29Z","timestamp":1789992689383,"version":"4.0.1"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: This study aimed to investigate the association between circulating monocyte subset profiles and carotid artery stenosis (CAS) severity and to examine their relationships with inflammatory and atherosclerosis-related parameters. Materials and Methods: This cross-sectional study included 73 adult patients who underwent carotid Doppler ultrasonography. Participants were classified according to internal CAS severity as &lt;50% (n = 44) or \u226550% (n = 29). Monocyte subsets were analyzed using flow cytometry and categorized as classical (CD14++CD16\u2212), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) monocytes. Serum MCP-1 concentrations were measured using an enzyme-linked immunosorbent assay. Clinical characteristics, biochemical parameters, inflammatory indices, and carotid intima\u2013media thickness (cIMT) were compared between the groups. Multivariate logistic regression analyses were performed to identify independent associations with significant stenosis. Results: Patients with CAS \u226550% exhibited significantly higher classical monocyte percentages and lower non-classical monocyte percentages than those with CAS &lt; 50% (p = 0.044 and p = 0.027, respectively). Intermediate monocyte percentages did not differ significantly between the groups. Significant stenosis was also associated with a higher white blood cell count, neutrophil count, systemic inflammatory response index, fibrinogen, and HbA1c levels. Non-classical monocyte percentages showed a significant inverse correlation with cIMT (r = \u22120.320, p = 0.006). In a multivariable model adjusted for age, sex, and systolic blood pressure, lower non-classical monocyte percentage was associated with significant CAS (OR 0.872, 95% CI 0.765\u20130.994; p = 0.040). However, this association was no longer statistically significant after further adjustment for fibrinogen, neutrophil count, and HbA1c, whereas fibrinogen remained independently associated with significant CAS. Conclusions: Lower circulating non-classical monocyte percentages were associated with significant CAS and inversely correlated with cIMT and inflammatory markers. However, the attenuation of this association after adjusting for inflammatory parameters suggests that monocyte subset distribution should be interpreted within the broader inflammatory context that accompanies advanced carotid atherosclerosis.<\/jats:p>","DOI":"10.3390\/medicina62091817","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:25:43Z","timestamp":1789986343000},"page":"1817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Monocyte Subsets with Carotid Artery Stenosis Severity"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5444-9116","authenticated-orcid":false,"given":"Levent","family":"Deniz","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Istanbul Training and Research Hospital, University of Health Sciences T\u00fcrkiye, 34098 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Derya","family":"Sonmez","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Istanbul Training and Research Hospital, University of Health Sciences T\u00fcrkiye, 34098 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7072-5985","authenticated-orcid":false,"given":"Mehmet Semih","family":"Cakir","sequence":"additional","affiliation":[{"name":"Department of Radiology, Istanbul Medical Faculty, Istanbul University, 34093 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1422-158X","authenticated-orcid":false,"given":"Eren","family":"Ozgur","sequence":"additional","affiliation":[{"name":"Department of Radiology, Istanbul Training and Research Hospital, University of Health Sciences T\u00fcrkiye, 34098 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Ozlem","family":"Akdogan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Istanbul Training and Research Hospital, University of Health Sciences T\u00fcrkiye, 34098 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5189-1534","authenticated-orcid":false,"given":"Zahide","family":"Adiyaman","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Kilis Public Health Laboratory, 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(2026). Treatment of carotid stenosis: An updated review. Front. Stroke, 5.","DOI":"10.3389\/fstro.2026.1849877"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/sji.12314","article-title":"The Role of Different Monocyte Subsets in the Pathogenesis of Atherosclerosis and Acute Coronary Syndromes","volume":"82","author":"Idzkowska","year":"2015","journal-title":"Scand. J. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1055\/a-2348-5697","article-title":"Monocyte Subsets in Cardiovascular Disease: A Biomarker Perspective","volume":"125","author":"Hristov","year":"2025","journal-title":"Thromb. Haemost."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1055\/a-2735-9854","article-title":"Pathophysiology of Atherosclerotic Carotid Disease","volume":"46","author":"Batarseh","year":"2026","journal-title":"Semin. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1111\/jdi.14048","article-title":"Non-classical monocytes frequency and serum vitamin D(3) levels are linked to diabetic foot ulcer associated with peripheral artery disease","volume":"14","author":"Hammad","year":"2023","journal-title":"J. Diabetes Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1161\/CIRCRESAHA.115.306256","article-title":"Macrophage Phenotype and Function in Different Stages of Atherosclerosis","volume":"118","author":"Tabas","year":"2016","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"530","DOI":"10.3109\/07853890.2014.931101","article-title":"Expression of monocyte subsets and angiogenic markers in relation to carotid plaque neovascularization in patients with pre-existing coronary artery disease and carotid stenosis","volume":"46","author":"Jaipersad","year":"2014","journal-title":"Ann. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Grosse, G.M., Schulz-Schaeffer, W.J., Teebken, O.E., Schuppner, R., Dirks, M., Worthmann, H., Lichtinghagen, R., Maye, G., Limbourg, F.P., and Weissenborn, K. (2016). Monocyte Subsets and Related Chemokines in Carotid Artery Stenosis and Ischemic Stroke. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040433"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zeynalova, S., Bucksch, K., Scholz, M., Yahiaoui-Doktor, M., Gross, M., Loffler, M., Melzer, S., and Tarnok, A. (2021). Monocyte subtype counts are associated with 10-year cardiovascular disease risk as determined by the Framingham Risk Score among subjects of the LIFE-Adult study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247480"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8748934","DOI":"10.1155\/2020\/8748934","article-title":"Blood Monocyte Phenotype Fingerprint of Stable Coronary Artery Disease: A Cross-Sectional Substudy of SMARTool Clinical Trial","volume":"2020","author":"Sbrana","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ejvs.2022.04.011","article-title":"Editor\u2019s Choice\u2014European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease","volume":"65","author":"Naylor","year":"2023","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_12","first-page":"e57941","article-title":"Characterization of Human Monocyte Subsets by Whole Blood Flow Cytometry Analysis","volume":"140","author":"Marimuthu","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9782594","DOI":"10.1155\/2019\/9782594","article-title":"Monocyte Subsets, Stanford-A Acute Aortic Dissection, and Carotid Artery Stenosis: New Evidences","volume":"2019","author":"Cifani","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Oh, E.S., Na, M., and Rogers, C.J. (2021). The Association Between Monocyte Subsets and Cardiometabolic Disorders\/Cardiovascular Disease: A Systematic Review and Meta-Analysis. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.640124"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sbrana, S., Cecchettini, A., Bastiani, L., Di Giorgi, N., Mazzone, A., Ceccherini, E., Vozzi, F., Caselli, C., Neglia, D., and Clemente, A. (2022). Blood M2-like Monocyte Polarization Is Associated with Calcific Plaque Phenotype in Stable Coronary Artery Disease: A Sub-Study of SMARTool Clinical Trial. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030565"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1161\/ATVBAHA.120.315886","article-title":"Nonclassical Monocytes (CD14dimCD16+) Are Associated With Carotid Intima-Media Thickness Progression for Men but Not Women: The Multi-Ethnic Study of Atherosclerosis-Brief Report","volume":"41","author":"Feinstein","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Abo-Aly, M., Shokri, E., Chelvarajan, L., Tarhuni, W.M., Tripathi, H., and Abdel-Latif, A. (2023). Prognostic Significance of Activated Monocytes in Patients with ST-Elevation Myocardial Infarction. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411342"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tomas, L., Prica, F., and Schulz, C. (2021). Trafficking of Mononuclear Phagocytes in Healthy Arteries and Atherosclerosis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.718432"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e21604","DOI":"10.1096\/fj.202100240R","article-title":"Rapid fall in circulating non-classical monocytes in ST elevation myocardial infarction patients correlates with cardiac injury","volume":"35","author":"Marsh","year":"2021","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Williams, H., Mack, C.D., Li, S.C.H., Fletcher, J.P., and Medbury, H.J. (2021). Nature versus Number: Monocytes in Cardiovascular Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179119"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1093\/cvr\/cvad069","article-title":"Monocyte heterogeneity in cardiovascular disease","volume":"119","author":"Ruder","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"441","DOI":"10.5551\/jat.49791","article-title":"Relationship between Circulating Inflammatory Monocytes and Cardiovascular Disease Measures of Carotid Intimal Thickness","volume":"27","author":"SahBandar","year":"2020","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ruiz-Limon, P., Ortega-Castro, R., Barbarroja, N., Perez-Sanchez, C., Jamin, C., Patino-Trives, A.M., Luque-Tevar, M., Ibanez-Costa, A., Perez-Sanchez, L., and de la Rosa, I.A. (2019). Molecular Characterization of Monocyte Subsets Reveals Specific and Distinctive Molecular Signatures Associated With Cardiovascular Disease in Rheumatoid Arthritis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01111"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1161\/ATVBAHA.121.316091","article-title":"Monocyte-Chemoattractant Protein-1 Levels in Human Atherosclerotic Lesions Associate With Plaque Vulnerability","volume":"41","author":"Georgakis","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/QAD.0000000000002389","article-title":"Plasma tissue factor and immune activation are associated with carotid intima-media thickness progression in treated HIV infection","volume":"34","author":"Hsu","year":"2020","journal-title":"AIDS"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"110624","DOI":"10.1016\/j.exger.2019.05.013","article-title":"Monocyte chemoattractant protein-1 (MCP-1) and fibroblast growth factor-21 (FGF-21) as biomarkers of subclinical atherosclerosis in women","volume":"124","author":"Basurto","year":"2019","journal-title":"Exp. Gerontol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nyarady, B.B., Dosa, E., Kohidai, L., Pallinger, E., Guban, R., Szonyi, A., Kiss, L.Z., and Bagyura, Z. (2024). Associations between Various Inflammatory Markers and Carotid Findings in a Voluntary Asymptomatic Population Sample. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179656"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Makarewicz-Wujec, M., Henzel, J., Kepka, C., Kruk, M., Wardziak, L., Trochimiuk, P., Parzonko, A., Dzielinska, Z., Demkow, M., and Kozlowska-Wojciechowska, M. (2021). Usefulness of MCP-1 Chemokine in the Monitoring of Patients with Coronary Artery Disease Subjected to Intensive Dietary Intervention: A Pilot Study. Nutrients, 13.","DOI":"10.3390\/nu13093047"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"de Carvalho, D.C., Fonseca, F.A.H., Izar, M.C.O., Silveira, A., Tuleta, I.D., do Amaral, J.B., Neves, L.M., Bachi, A.L.L., and Franca, C.N. (2022). Monocytes presenting a pro-inflammatory profile persist in patients submitted to a long-term pharmacological treatment after acute myocardial infarction. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.1056466"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Tsioufis, P., Theofilis, P., Tsioufis, K., and Tousoulis, D. (2022). The Impact of Cytokines in Coronary Atherosclerotic Plaque: Current Therapeutic Approaches. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415937"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/clc.24005","article-title":"Synergistic role of circulating CD14++CD16+ monocytes and fibrinogen in predicting the cardiovascular events after myocardial infarction","volume":"46","author":"Zhang","year":"2023","journal-title":"Clin. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Afanasieva, O.I., Tyurina, A.V., Klesareva, E.A., Arefieva, T.I., Ezhov, M.V., and Pokrovsky, S.N. (2022). Lipoprotein(a), Immune Cells and Cardiovascular Outcomes in Patients with Premature Coronary Heart Disease. J. Pers. Med., 12.","DOI":"10.3390\/jpm12020269"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Vellasamy, D.M., Lee, S.J., Goh, K.W., Goh, B.H., Tang, Y.Q., Ming, L.C., and Yap, W.H. (2022). Targeting Immune Senescence in Atherosclerosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113059"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Han, Z., Liu, Q., Li, H., Zhang, M., You, L., Lin, Y., Wang, K., Gou, Q., Wang, Z., and Zhou, S. (2023). The role of monocytes in thrombotic diseases: A review. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1113827"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101663","DOI":"10.1016\/j.ajpc.2026.101663","article-title":"A novel monocyte-based biomarker of cardiovascular risk: Comparison with traditional cardiovascular risk calculators","volume":"29","author":"Almarri","year":"2026","journal-title":"Am. J. Prev. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"583398","DOI":"10.2147\/VHRM.S583398","article-title":"Associations of High-Sensitivity Cardiac Troponin T, D-Dimer, and N-Terminal Pro-B-Type Natriuretic Peptide with Subclinical Cardiovascular Dysfunction in the General Population: A Retrospective Cross-Sectional Study","volume":"22","author":"Jakubiak","year":"2026","journal-title":"Vasc. Health Risk Manag."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/9\/1817\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:29:38Z","timestamp":1789990178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/9\/1817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["medicina62091817"],"URL":"https:\/\/doi.org\/10.3390\/medicina62091817","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}