{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:40:13Z","timestamp":1793814013911,"version":"4.6.1"},"reference-count":18,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Type 2 diabetes mellitus (DM) and carotid atherosclerosis are established risk factors for cardiovascular disease (CVD). However, their relative and combined prognostic significance in individuals without known CVD remains uncertain. This study aimed to evaluate the independent and combined associations of carotid plaques and DM with cardiovascular events and mortality in a high-cardiometabolic-risk primary prevention cohort. Methods: This prospective cohort study followed 6138 participants (3571 men [57%] and 2567 women [43%]; median age 53 years, IQR 48\u201358) enrolled in the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program from 2006 to 2023. All individuals underwent clinical assessment and carotid ultrasonography. Participants were stratified by DM status and the presence of carotid plaques. Associations with cardiovascular events, major adverse cardiovascular events (MACE, including non-fatal ischaemic stroke, non-fatal myocardial infarction, and cardiovascular death), and all-cause mortality were evaluated using Cox proportional hazards models. Results: During follow-up (median 6.5 years, IQR 4.5\u20139.0), 954 participants (16%) experienced composite cardiovascular events (MACE, including non-fatal ischaemic stroke, non-fatal myocardial infarction, and cardiovascular death). Bilateral carotid plaques were more common in individuals with cardiovascular events (23.3% vs. 19.4%; p = 0.007). Individuals with both DM and carotid plaques had the highest risk of MACE (HR = 1.696; 95% CI: 1.346\u20132.136; p &lt; 0.001), myocardial infarction (MI; HR = 4.089; 95% CI: 1.590\u201310.516; p = 0.003), and all-cause mortality (HR = 1.802; p = 0.015). The presence of carotid plaques without DM was independently associated with increased risk of MACE (HR = 1.234; 95% CI: 1.062\u20131.433; p = 0.006) and MI (HR = 2.492; 95% CI: 1.176\u20135.278; p = 0.017), but not all-cause mortality (HR = 0.986; 95% CI: 0.689\u20131.413; p = 0.941). In contrast, DM without carotid plaques was not significantly associated with any outcome examined. Conclusions: In this high-cardiometabolic-risk primary prevention cohort, carotid plaques were independently and more strongly associated with cardiovascular outcomes than diabetes alone. Individuals with both carotid plaques and diabetes showed the highest observed risk of adverse cardiovascular events and all-cause mortality. These findings are associational and apply to a high-risk metabolic syndrome cohort; extrapolation to the general population requires further study. The results support the prognostic value of carotid plaque assessment as an adjunctive tool in cardiovascular risk evaluation.<\/jats:p>","DOI":"10.3390\/jcm15145695","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:14:27Z","timestamp":1784621667000},"page":"5695","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Carotid Plaques and Type 2 Diabetes as Predictors of Cardiovascular Events and Mortality: Insights from the LitHiR Prospective Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1471-9131","authenticated-orcid":false,"given":"Vilma","family":"Dzenkeviciute","sequence":"first","affiliation":[{"name":"Clinic of Internal and Family Medicine, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, LT-03101 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadas","family":"Adomavicius","sequence":"additional","affiliation":[{"name":"Clinic of Internal and Family Medicine, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, LT-03101 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9442-4539","authenticated-orcid":false,"given":"Gabriele","family":"Tarutyte","sequence":"additional","affiliation":[{"name":"Department of Research and Innovation, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4362-8143","authenticated-orcid":false,"given":"Egidija","family":"Rinkuniene","sequence":"additional","affiliation":[{"name":"Clinic of Cardiac and Vascular Diseases, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vytautas","family":"Kasiulevicius","sequence":"additional","affiliation":[{"name":"Clinic of Internal and Family Medicine, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, LT-03101 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-9803","authenticated-orcid":false,"given":"Jolita","family":"Badariene","sequence":"additional","affiliation":[{"name":"Clinic of Cardiac and Vascular Diseases, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","first-page":"79","article-title":"Associations Between Carotid Artery Plaque Burden, Plaque Characteristics, and Cardiovascular Events: The ARIC Carotid Magnetic Resonance Imaging Study","volume":"6","author":"Brunner","year":"2021","journal-title":"JAMA Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.echo.2020.04.021","article-title":"Recommendations for the Assessment of Carotid Arterial Plaque by Ultrasound for the Characterization of Atherosclerosis and Evaluation of Cardiovascular Risk: From the American Society of Echocardiography","volume":"33","author":"Johri","year":"2020","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ihle-Hansen, H., Vigen, T., Berge, T., Walle-Hansen, M.M., Hagberg, G., Ihle-Hansen, H., Thommessen, B., Ariansen, I., R\u00f8sj\u00f8, H., and R\u00f8nning, O.M. (2023). Carotid plaque score for stroke and cardiovascular risk prediction in a middle-aged cohort from the general population. J. Am. Heart Assoc., 12.","DOI":"10.1161\/JAHA.123.030739"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1016\/S0140-6736(12)60441-3","article-title":"Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): A meta-analysis of individual participant data","volume":"379","author":"Lorenz","year":"2012","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.amjcard.2018.01.001","article-title":"Usefulness of Carotid Plaques as Predictors of Obstructive Coronary Artery Disease and Cardiovascular Events in Asymptomatic Individuals with Diabetes Mellitus","volume":"121","author":"Jeevarethinam","year":"2018","journal-title":"Am. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cardoso, C.R.L., Salles, G.C., Leite, N.C., and Salles, G.F. (2019). Prognostic impact of carotid intima-media thickness and carotid plaques on the development of micro- and macrovascular complications in individuals with type 2 diabetes: The Rio de Janeiro type 2 diabetes cohort study. Cardiovasc. Diabetol., 18.","DOI":"10.1186\/s12933-019-0809-1"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"\u00d6stgren, C.J., Otten, J., Festin, K., Anger\u00e5s, O., Bergstr\u00f6m, G., Cederlund, K., Engstr\u00f6m, G., Eriksson, M.J., Eriksson, M., and Fall, T. (2023). Prevalence of atherosclerosis in individuals with prediabetes and diabetes compared to normoglycaemic individuals-a Swedish population-based study. Cardiovasc. Diabetol., 22.","DOI":"10.1186\/s12933-023-01982-6"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Genkel, V., Kuznetsova, A., Lebedev, E., Salashenko, A., Savochkina, A., Nikushkina, K., Pykhova, L., Sumerkina, V., and Shaposhnik, I. (2023). Carotid total plaque area as an independent predictor of short-term subclinical polyvascular atherosclerosis progression and major adverse cardiac and cerebrovascular events. Ther. Adv. Cardiovasc. Dis., 17.","DOI":"10.1177\/17539447231194861"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Liu, Y., Kong, Y., Yan, Y., and Hui, P. (2024). Explore the value of carotid ultrasound radiomics nomogram in predicting ischemic stroke risk in patients with type 2 diabetes mellitus. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1357580"},{"key":"ref_10","first-page":"12","article-title":"New atherogenic index for the prediction of carotid atherosclerosis based on the non-ultrasensitive C-reactive protein\/HDL ratio","volume":"36","author":"Tormos","year":"2024","journal-title":"Clin. Investig. Arterioscler."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"D\u017eenkevi\u010di\u016bt\u0117, V., Adomavi\u010dius, T., Tarutyt\u0117, G., Rink\u016bnien\u0117, E., Kasiulevi\u010dius, V., and Badarien\u0117, J. (2024). Carotid Plaques and Hypertension as Risk Factors for Cardiovascular Disease and All-Cause Mortality in Middle-Aged Adults. J. Clin. Med., 13.","DOI":"10.3390\/jcm13102804"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","article-title":"2018 ESC\/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH)","volume":"39","author":"Williams","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000097034","article-title":"Mannheim Carotid Intima-Media Thickness Consensus (2004\u20132006): An Update on Behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006","volume":"23","author":"Touboul","year":"2007","journal-title":"Cerebrovasc. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.atherosclerosis.2011.06.044","article-title":"Carotid plaque, compared with carotid intima-media thickness, more accurately predicts coronary artery disease events: A meta-analysis","volume":"220","author":"Inaba","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Liu, Z., Zhang, L., Sun, B., and Ding, Y. (2024). Association of cardiovascular risk factors and intraplaque neovascularization in symptomatic carotid plaque. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1442656"},{"key":"ref_16","first-page":"14","article-title":"Comprehensive analysis of risk factors for carotid plaque in type 2 diabetes mellitus: A meta-analysis","volume":"10","author":"Yang","year":"2023","journal-title":"Glob. J. Med. Health Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Feraldi, A., Zarulli, V., Buse, K., Hawkes, S., and Chang, A.Y. (2025). Sex-disaggregated data along the gendered health pathways: A review and analysis of global data on hypertension, diabetes, HIV, and AIDS. PLoS Med., 22.","DOI":"10.1371\/journal.pmed.1004592"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Noflatscher, M., Schreinlechner, M., Sommer, P., Kerschbaum, J., Berggren, K., Theurl, M., Kirchmair, R., and Marschang, P. (2018). Influence of Traditional Cardiovascular Risk Factors on Carotid and Femoral Atherosclerotic Plaque Volume as Measured by Three-Dimensional Ultrasound. J. Clin. Med., 8.","DOI":"10.3390\/jcm8010032"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5695\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:48:58Z","timestamp":1784623738000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5695"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":18,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15145695"],"URL":"https:\/\/doi.org\/10.3390\/jcm15145695","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]}}}